THE HEALING PROCESS IN WOUNDS OF THE BRAIN
ARCHIE H. BAGGENSTOSS, JAMES W. KERNOHAN
Section on Pathologie Anatomy, Mayo Clinic
AND
JOHN P. DRAPIEWSKI
Fellow in Pathology, Mayo Foundation, Rochester, Minnesota
Although there hâve been nurr.erous studies on the healing of wounds of the
brain in expérimental animais1""10, relatively few observations hâve been recorded
for man. Single case reports of wcunds of the brain hâve been rr^ade by Ziegler11,
Von Kahlden12, Chenzinski13 and Courville and Kimball14. Pfeifer16 studied
wounds of the brain in three cases. Thèse wounds were made by a trocar during
an operative search for tumors of the brain. Wilson16 reported a study of ventricular puncture wounds in two cases of gênerai paresis. Foerster and Penfield17
reported the results of examination of excised cérébral scars which had been
removed for the treatment of traumatic epilepsy. The most extensive study
of the reaction of the human brain to injuries of various types was made by Rand
and Courville18-20. Most of their subjects, however, had sustained injuries of
the brain such as contusions and hemorrhages. Penetrating wounds comparable
to those to be reported in the présent paper were infrequent.
MATERIAL AND METHODS
The présent study was based on seventy selected cases in which ventricular
puncture wounds had been made in the course of ventriculographic studies for
the purpose of diagnosis and location of tumors of the brain. In most cases, the
brain at necropsy had shown évidence of varying degrees of increased intracranial pressure, such as flattening of the convolutions, narrowing of the sulci
and in some instances herniation of the cerebellar tonsils into the foramen magnum. Thèse signs of increased intracranial pressure were the resuit of expanding
lésions, with or without associated edema, within the brain. In some instances,
the tumor had obstructed the ventricular System and produced internai hydrocephalus of varying degrees. The âge distribution of the patients is given in
table 1. In table 2, the cases are arranged according to the âge of the puncture
wound, which varied from a few hours to seven years. As can be seen from
the table, there were numerous examples of wounds from one day or less to two
weeks of âge but examples of wounds older than two weeks were more difficult
to obtain.
Longitudinal and cross sections of the wounds were taken in both the white and gray
matter. The sections werefixedin Cajal's fixative, Zenker's solution and solution of formaldehyde U. S. P., diluted 1:10. The following staining methods were employed: Cajal's
gold sublima te method for astrocytes; Penfield's and McCarter's modifications of Hortega's
silver imprégnation method for oligodendroglia andmicroglia; Orlandi, Bodian and Perdrau
silver imprégnation methods; Mallory-Heidenhain (azoearmine) ; Mallory phosphotungstic
acid hematoxylin; cresyl violet; sudan III; hematoxylin and eosin; Weigert's stain for
myelin sheaths and an iron stain.
333
334
A. H. BAGGENSTOSS, J. W. KERNOHAN AND J. F. DRAPIEWSKI
OBSERVATIONS
For the sake of brevity, a gênerai description as a group will be given of wounds
of the same âge or approximately the same âge. It should be pointed out,
however, that in some instances, variations within a group of the same âge were
greater than variations between wounds of différent âges.
Age of wound one day or less (twelve cases). In puncture wounds studied one
day or less after they were made, hemorrhage, together with necrosis of ail
TABLE 1
AGE OF PATIENTS
AGE
CASES
ytars
0- 9
10-19
20-29
30-39
40-49
50-59
9
15
12
11
18
5
TABLE 2
CASES ACCOEDING TO AGE OF WOUND
AGE OF WOUND
1 day or less
2 days
3 days
4 days
5 days
6 days
7 days
8 days
9 days
10 days
12 days
13 days
14 days
CASES
12
5
5
6
3
6
3
4
3
1
3
3
2
AGE OF WOUND
CASES
19 days
20 days
23 days
25 days
30 days
45 days
55 days
58 days
75 days
80 days
196 days
206 days
7 years
cellular éléments in the center of the wound, was the most prominent feature.
Surrounding a central région of hemorrhage and necrosis there was a wide zone
(approximately 1.5 to 2 mm.) of intercellular and pericellular edema in which the
capillaries were dilated and congested and there were numerous focal and
perivascular hemorrhages (fig. 1). Occasionally necrosis of the walls of small
arteries and arterioles and a perivascular exudation of fibrin were observed in
this zone. Polymorphonuclear cells varied in number in thèse wounds and were
frequently observed to contain lipoid droplets. Phagocytosis of degenerating
nerve cells and myelin sheaths by polymorphonuclear cells was apparent in many
THE HEALING OF WOUNDS OF THE BRAIN
335
wounds. A few large mononuclear cells were présent but compound granular
corpuscles were not observed.
In the central hemorrhagic portion of the wound and its immédiate vicinity
degenerative changes of the neuroglia and nerve cells were prominent. Among
the glial éléments ail stages of degeneration from early changes such as acute
swelling of the oligodendroglia (edema) and swelling of astrocytes to complète
necrosis could be observed. Clasmatodendrosis (Cajal) or ameboid change
(Alzheimer) had occurred. Occasionally astrocytes were seen in which the cell
body was disintegrating while the processes attached to capillaries were still
intact. Microglial cells in stages transitional to compound granular corpuscles
were not observed.
FIG. 1. PUNCTURE WOUND OF ONE DAY'S DUBATION
The central hemorrhagic and necrotic portion has fallen out but the zone of edema and
perivascular hemorrhages is well shown (hematoxylin and eosin X 23J).
The nerve cells were the seat of swelling and the cytoplasm had become intensely acidophilic. The most prominent nuclear change was karyolysis. Complète disappearance of the nuclei was a fréquent phenomenon. Pyknosis and
karyorrhexis were common in the necrotic central portion of the wound but
were observed less frequently in the edematous peripheral zone. Swelling and
fragmentation of myelin sheaths and axons were also observed.
Two days (five cases). Wounds of this duration had much the same appearance as those of one day or less. In the zone of edema adjacent to the puncture,
congestion and perivascular hemorrhages were more pronounced than in wounds
of one day. Thrombosis was uncommon, however. The endothelial cells
lining the capillaries were frequently swollen. Perivascular, interstitial and
pericellular edema was also more pronounced. The line of démarcation between
336
A. H. BAGGENSTOSS, J. W. KERNOHAN AND J. F. DRAPIEWSKI
the zone of edema and normal brain was often sharp and distinct. Polymorphonuclear cells, some of which contained vacuoles and lipoid droplets, had
increased in number in the path of the wound and in the surrounding dégénéra ting brain as well. A few mononuclear cells which contained lipoid droplets
were also présent. Degenerative changes in the neuroglia and nerve cells were
as pronounced as in wounds of one day (fig. 2a). There were observed in the
edematous zone numerous oval, spherical and irregular acidophilic masses which
appeared to be remnants of nerve cells and degenerating myelin sheaths.
FIG. 2. WOUNDS OF TWO AND THREE DAYS' DUKATION
a. Degenerative changes (clasmatodendrosis) in astrocytes in a wound of two days
(Cajal gold sublimate X 500); 6, polymorphonuclear leukocytes containing lipoid droplets
in a wound of three days (hematoxylin and eosin X 950 [oil immersion]).
Three days, (Jive cases). Wounds of this âge were similar to those already
described but deserve particular mention because they were the first to reveal the
so-called compound granular corpuscles. Thèse lipoid or fat-laden phagocytes
were few at this stage and were gênerai! y in close relation to capillaries or larger
blood vessels. Polymorphonuclear cells were much more numerous than compound granular corpuscles, however, and many of them contained lipoid droplets
(fig. 2b). Mononuclear cells were also présent but microglial cells were not
increased in number nor were transition forms between microglia and compound
granular corpuscles observed. Mitotic figures were seen occasionally in the
THE HEALING OF WOUNDS OF THE BRAIN
337
zone of edema but the identity of the cells containing them could not
be established.
Four days (six cases). In wounds of this âge, endothelial prolifération in the
walls of capillaries and swollen or hypertrophied forms of astrocytes (gemâstete
glia) were observed for the first time. In wounds of less duration, swelling of
endothelial cells was often observed but actual prolifération of endothelial cells
as indicated by mitotic figures and capillary walls possessing more than a single
layer of endothelial cells had not been seen. The so-called gemâstete glia consisted of astrocytes with an increased amount of acidophilic, hyaline-appearing
cytoplasm, retracted processes and oval eccentric nuclei. The changes in thèse
cells were interpreted as a régressive but not an irréversible process.
Aside from thèse new phenomena there were increased numbers of compound
FIG. 3. SWOLLEN MICBOGLIA INTEBPEETED AS A STAGE TEANSITIONAL TO COMPOUND
GBANULAR CORPUSCLES (HORGEGA'S SILVER CARBONATE FOR MICBOGLIA X 500)
granular corpuscles. Thèse cells appeared to be derived from the proliferating
endothelial cells associated with the capillaries and also from the adventitial
cells of larger vessels. We frequently observed cells which contained phagocytosed pigment and lipoid droplets although they were still attached to the
walls of vessels. Other cells, apparently derived from capillaries and the adventitia of larger vessels, were found in ail stages transitional to compound granular corpuscles. Microglial cells which were somewhat hypertrophied and may
hâve represented stages transitional to that of the compound granular corpuscles
were also observed in a wound of this âge (fig. 3). Microglial cells of this type,
however, were relatively few and it did not seem that many of the compound
granular corpuscles were derived from them. Polymorphonuclear cells were
also increased in numbers and appeared to be active in phagocytosis.
338
A. H. BAGGENSTOSS, J. W. KERNOHAN AND J. F. DHAPIEWSKI
Five to seven days inclusive (twelve cases). Wounds varying in âge from five to
seven days, inclusive, will be considered together because of their similarity.
They presented, in gênerai, much the same appearance as the wounds already
described. Prolifération of endothelial cells of the capillaries, which was first
observed distinctly in wounds of four days' duration, had become a progressively
more prominent feature (fig. 4a). Mitotic figures were présent, the walls of the
capillaries were thickened and the capillaries appeared to be increased in number.
In some wounds, the endothelial prolifération had been so rapid that multinucleated giant cells had formed. Scavenger cells or phagocytes laden with
lipoid droplets and hemosiderin were numerous in wounds of this âge. They
appeared to be derived largely from capillary endothelium and the adventitia
of larger vessels as well as from mononuclear blood cells. Polymbrphonuclear
leukocytes were still numerous and in some instances could be observed traversing capillary walls. Many of them contained lipoid droplets and were found in
perivascular spaces. The larger lipoid-laden phagocytes (compound granular
corpuscles), however, ail appeared to possess a single spherical or oval nucleus.
Occasional lymphocytes were observed and rarely a fibroblast.
Among the neuroglial éléments, the only significant change was an apparent
increase of the numbers of "gemâstete glia," including binucleated and multinucleated forms, in the zone of edema. Although thèse cells were fairly numerous in wounds of this âge, actual prolifération by mitosis or amitotic division
was not observed. Occasional mitotic figures were observed in cells not in
relation to capillaries. Thèse could not be identified with certainty but may
hâve been microglial cells. In sections stained by Orlandi's and Bodian's silver
stains many nerve fibers were observed to be swollen and fragmented. Others
were observed in which the axis cylinders had bulbous ends, corkscrew deformities and other irregularities.
Eight to ten days, inclusive (eight cases). Thèse wounds differed from those of
less duration in that prolifération of capillaries and endothelial cells was more
pronounced and significant numbers of fibroblasts and collagen fibrils were
noted for the first time. The capillaries and fibroblasts were directed radially
toward the hemorrhagic and necrotic central portion of the wound, which contained large numbers of compound granular corpuscles. There was beginning
invasion of this central portion by capillaries and fibroblasts : a process of organization of exudates similar to that frequently observed elsewhere in the body but
much less vigorous (fig. 4b). There was less évidence of edema at the edge of
the wounds than previously. Polymorphonuclear and mononuclear leukocytes,
active in phagocytosis, were observed and lymphocytes, usually in perivascular
spaces, were présent in increased numbers. There were numerous cells transitional between lymphocytes and fully developed compound granular corpuscles.
Hypertrophied astrocytes, including multinucleated forms as well as unipolar
and bipolar forms, were présent in considérable numbers. The fact that binucleated and multinucleated forms were observed probably indicated prolifération but amitotic division was not observed and fusion of pre-existing
THE HEALING OF WOUNDS OF THE BRAIN
339
astrocytes could not be ruled out. Acute swelling of oligodendroglia could
still be observed in wounds of this âge. The only changes of nerve cells and
fibers were degenerative. Satellitosis and neuronophagia were observed.
FIG. 4. WOUNDS OF SEVEN AND EIGHT DAYS' DURATION
a. Prolifération of endothelial cells in a wound of seven days; note mitosis (hematoxylin
and eosin X 320) ; b, capillaries and scavenger cells at edge of a wound of eight days (hematoxylin and eosin X 135).
Twelve to fourtcen days, inclusive (eight cases). In wounds of this âge, the
zone of edema and perivascular hemorrhages had been largely replaced by a
zone of capillaries and prcliferating fibroblasts (fig. 5a and b). Fibroblasts,
340
A. H. BAGGENSTOSS, J. W. KERNOHAN AND J. F. DRAPIEWSKI
which were first observed in wounds of eight to ten days' duration, were more
numerous in thèse older wounds. Thèse cells were generally in close relation
to capillaries and were interspersed between the scavenger cells. Together
with the capillaries they could be seen invading the central portion of the wound,
which usually was partly filled by scavenger cells. Thèse phagocytes had
reached their greatest numbers in wounds of this âge and had replaced the
necrotic débris to a considérable extent. The capillary and fibroblastic reaction
was observed to be more vigorous in the cortex than in the white matter. This
l-'i'j. û. A WOUND OF TWELVE DAYS
a. The central necrotic région and the capillary zone are shown (hematoxylin and eosin
X 24); 6, prolifération of endothelial cells of the capillaries (hematoxylin and eosin X 135).
différence in the degree of reaction had not been observed in earlier wounds. By
the use of silver stains such as the Perdrau, a reticular network, formed by the
capillaries and collagen and reticular fibers at the edge of the wound, was well
demonstrated. Lymphocytes were more numerous in the capillary zone in
wounds of this âge while polymorphonuclear cells were diminished in number.
Plasma cells were first observed in wounds of this duration and were occasionally
binucleate. Numerous hypertrophied astrocytes were observed in the tissue
peripheral to the zone of capillaries. In this peripheral zone nerve cells were
few and degenerative changes were not as prominent as in wounds of shorter
duration.
THE HEALING OP WOUNDS OF THE BRAIN
341
Nineteen to twenty-five days, inclusive (JLve cases). In wounds of this âge, three
fairly distinct zones could be distinguished (fig. 6a). Thèse consisted of a
central région of necrotic débris, which had been partly evacuated and replaced
by compound granular corpuscles; a capillary zone or zone of granulation tissue,
which was invading the central région and also served to wall it off; and a
peripheral zone of hypertrophied astrocytes.
The central portion of the wound had been partially emptied of its necrotic
débris and in some instances there remained only a cystic space which contained
lipoid-laden phagocytes at the edge. In the zone of capillaries or granulation
tissue, fibroblastic prolifération was more évident than in earlier wounds but
was still relatively weak and was confined to the edge of the wound. The
FIG. 6. WOUND OF TWENTY-THREE DAYS
a. The three zones are shown (hematoxylin and eosin X 26); b, from the edge of the
wound shown in a (Perdrau silver stain to show capillaries and reticular network X 100).
endothelial and fibroblastic prolifération was niore vigorous in the cortex thàn
in the white matter. The fibroblasts were generally in close relation to the
capillaries and reticular and collagen fibrils were more numerous than in earlier
wounds (fig. 6b). Many compound granular corpuscles filled the meshes formed
by capillaries and reticular fibers while others partially filled the central portion.
Lymphocytes were more numerous in wounds of this âge in perivascular spaces
and in the capillary zone about the cavity. Plasma cells were also somewhat
more numerous and polymorphonuclear leukocytes were greatly diminished
in number.
Peripheral to the zone of capillaries numerous hypertrophied astrocytes were
observed (fig. la and b). In almost ail of thèse cells the nuclei were eccentric
342
A. H. BAGGENSTOSS, J. W. KERNOHAN AND J. F. DRAPIEWSKI
and generally flattened against one side of the cell. Binucleate forms were
fairly comiron but a mitotic division was not observed and the cells did not appear
to be greatly increased in number. There was no question, however, of their
increase in size. A few of them could be observed close to the edge of the cavity
but rcost of them were definitely peripheral to the capillary zone.
Thirty to fifty-eight days, inclusive (four cases). In wounds of this duration
endothelial prolifération and fibroblastic prolifération were not as pronounced
as in earlier wounds but the formation of reticular and collagen fibrils had
progressed. This process was also more vigorous in the cortex than in the white
rr.atter. The capillaries were generally arranged radially at the edge of the
FIG. 7. WOUND OF TWENTY-THREË DAYS TO SHOW THE HYPEBTBOPHIED ASTBOCYTES
a. (hematoxylin and eosin X 145); b, (Cajal gold sublimate X 500)
wound but many of those in the cavity appeared to run longitudinal 1 y and this
was also true of the reticular and collagen fibrils. The removal of the necrotic
débris in the central portion of the wound seemed to be almost complète in most
instances. A loose network of capillaries and reticular and collagen fibrils, with
lipoid and pigment-laden phagocytes in the meshes, had replaced the necrotic
central portion to a large extent and in most instances (fig. 8a). The latter,
however, was not filled completely by capillaries or connective tissue but generally possessed a central cavity or space. In one wound of fifty-eight days,
however, there were still islands of necrotic brain présent in the cavity and numbers of polymorphonuclear cells were observed. In the capillary zone of ail
THE HEALING OF WOUNDS OF THE BBAIN
343
thèse wounds, scavenger cells and lymphocytes were the most numerous cellular
éléments. Plasma cells were also présent but not numerous.
l'i<J. b. \YuLNU~ ur PlPTY-PlVB AND ElGHTY DAYS
a. Wound of fifty-five days in cortex. Note organization of central portion (to left)
(heraatoxylin and eosin X 115) ; 6, wound of eighty days in white matter; note the comparative lack of réaction of connective tissue (hematoxylin and eosin X 115).
Peripheral to the zone of capillaries and continuous with normal brain there
was a zone of hypertrophied astrocytes (gemâstete glia). Some of thèse cells
344
A. H. BAGGENSTOSS, J. W. KERNOHAN AND J. F. DEAPIEWSKI
were enmeshed by capillaries and reticular fibrils at the outer edge of the capillary
zone but most of them were peripheral to this zone. They did not appear to be
increased in number or to possess any particular alinement or orientation in
relation to the wound. Other cells in this région appeared to be diminished in
number although degenerative changes in nerve cells were rarely observed in
wounds of this âge. The ependymal cells in the ventricular portion of the
wound were flattened or altogether missing and there was only slight évidence
of their régénération. This was also true of previously described wounds of
shorter duration.
Seventy-five to eighty days, inclusive (two cases). In wounds of this duration,
there was no évidence of an increase of capillaries or collagenous fibers. The
capillary zone was actually narrower than in some wounds of less duration. The
central portion was almost completely evacuated of the necrotic débris and was
only partly filled by loosely interwoven capillaries and connective tissue. There
was more connective tissue in the cortex than in the white matter and in some
sections of the latter, the wounds resembled old infarcts in the almost complète
lack of response of connective tissue (fig. 8&). There was no apparent increase
of the number of astrocytes nor was there any particular arrangement of those
cells.
One hundred and ninety-six to two hundred and six days (two cases). Thèse
wounds differed from those already described chiefly in the increased number of
hypertrophied astrocytes présent in the cortex. Thèse cells were présent in
greatly increased numbers in the zone peripheral to the capillaries and there was
more intermingling with collagenous fibers at the edge of the capillary zone
than in wounds of shorter duration. In the cortex thèse wounds were distinguished also by the présence of islands of hypertrophied and multinucleated
astrocytes and their fibers scattered irregularly throughout the core of connective
tissue (fig. 9). In some sections astrocytes were so numerous that there could
be no question that prolifération had occurred. Many of thèse astrocytes were
very large and had small, hairlike processes—the piloid astrocytes of Penfield.
Careful examination of thèse islets of glial prolifération revealed the fact that
they were arranged about capillaries, arterioles and venules together with
numerous compound granular corpuscles. Thèse cells were numerous throughout the wound and were also associated with islands of degenerating brain tissue.
In the white matter, there was hardly any évidence of mesodermal reaction.
For the most part, there were only cystic spaces surrounded by a zone of hypertrophied astrocytes.
Seven years (one case). Unfortunately only one case in which there was a
puncture wound of more than a year's duration was available for study. The
patient was a girl, aged fifteen years, who had had ventriculographic studies
seven years before her death. The wound differed in a number of ways from
those already described. The central portion of the wound was filled in, rather
loosely, by bundles of collagenous fibers. There were no longer any phagocytic
cells, lymphocytes or plasma cells présent. There was no capillary zone as
such nor was there any increase of astrocytes. On the contrary, there was a
THE HEALING OF WOUNDS OF THE BRAIN
345
diminution of the cellular content of the tissue about the wound—a zone of
atrophy (fig. 10).
FIG. 9. WOUND OF CORTEX OF ONE HTJNDRED AND NINETY-SIX DAYS' DURATION
Intermingling of astrocytes and fibrous connective tissue (hematoxylin and eosin X 160)
FIG. 10. WOUND OP WHITE MATTER OF SEVEN YEARS' DURATION
Loosely woven connective tissue in center with atrophy of surrounding brain
(hematoxylin and eosin X 170).
In another case in which the patient was a man, aged thirty-one years, who
had had a skull fracture twenty-five years before, there was available for study
346
A. H. BAGGENSTOSS, J. W. KERNOHAN AND J. F. DRAPIEWSKI
an encephalomalacic cyst 4 cm. in diameter near the site of the ancient fracture.
There was a very thin layer of piloid astrocyte fibers but there was no reaction
in the surrounding brain.
COMMENT
In this study of the reaction of the brain to injury one is amazed by the lack
of vigor displayed in the healing process. This is especially true when one compares the reaction of the brain with that of other organs of the body. The slow
tempo of the reparative process is emphasized by the fact that dead brain tissue,
as well as phagocytic cells, was still présent in wounds more than six months of
âge. Similar observations hâve been made by Ziegler11, who studied a stab
wound of the brain two years after it was made; by Chenzinski13, who studied a
gunshot wound twenty-seven months after the injury and by Courville and
Kimball14, who studied a gunshot wound twenty-two years after it was made.
Ziegler and Courville and Kimball expressed the opinion that the process of
disintegration and that of repair were probably continuous in some instances.
The lack of reparative power in the brain probably résides in the character
of the highly differentiated cells that are destroyed, the fragility of the framework and the scarcity of mesodermal éléments in it, and finally, in the paculiarity
of the vascular pattern. It may be that the increased intracranial pressure
which was présent in most of thèse cases exerted an inhibiting influence on the
reparative process. Nevertheless, the other reports of wounds of the brain
quoted earlier in this paragraph also emphasize the slowness of the healing
process, although increased intracranial pressure had not previously been présent
in thèse cases. It is well to emphasize that when repair does take place, the
prédominant rôle is played by mesodermal éléments—capillaries, endothelium,
fibroblasts and leukocytes.
It was anticipated that repair would be more vigorous among children than
among adults. A careful comparison of observations in the différent âge groups
failed to detect any significant différences, however.
The rôle of the astrocytes in the reaction of the brain to injury has been a
live subject for many investigators21. According to Weigert22 and Mùller23,
thèse cells reacted in pathologie processes exactly like typical connective tissue.
From our own observations, however, it appears that they play a very minor
rôle in the healing process. The astrocytes were more résistant to injury than
nerve cells in the earlier stages of the wound but did not reveal any évidence of
prolifération until long after the infiammatory reaction had subsided. It was
not until very late (196 day wound) that one could be certain that prolifération
had occurred. In earlier wounds, abnormal astrocytes were often présent in
considérable numbers but only in a zone peripheral to the actual région of repair.
We were unable to detect any radial arrangement or alinement of the astrocytes
toward the connective tissue of the healed wound such as has been described
by Penfield.24 This may be due in part to the fact that in very few of our cases
were the wounds of more than six months' duration. Presumably, contraction
of the scar and the concomitant "pull" on the astrocytes would be detected only
in older wounds.
THE HEALING OF WOUNDS OF THE BRAIN
347
The question of the source of the compound granular corpuscles (phagocytes,
scavenger cells) has also been of considérable interest to neuropathologists for a
long time. No attempt will be made to review the various viewpoints or the
experiments and observations on which they were based. It will be sufficient
to point out that in this study the compound granular corpuscles were first
observed in wounds of three days, that they reached their greatest number in
wounds of ten to fourteen days and that they were still présent in wounds more
than six months of âge. From observations of thèse wounds, the microglial
cells appeared to play a very small part in the production of the compound
granular corpuscles. Microglial cells were not increased in number and only
occasionally were there observed microglial cells which could be considered as
transitional to compound granular corpuscles. Most of the latter appeared to
arise from endothelial cells associated with the capillaries, from adventitial cells
of larger vessels and from mononuclear cells of the circulating blood. In wounds
of eight days and more, lymphocytes may hâve been an important source of
thèse cells, as many transitional forms between the small lymphocytes and the
large phagocytes distended by lipoid droplets could be observed. There was
also évidence that polymorphonuclear leukocytes were active in phagocytosis,
especially during the early days of the wound. The possibility that the lipoid
droplets found in thèse cells were évidence of cellular degeneration rather than
of phagocytosis must of course be considered. The compound granular corpuscles did not appear to be derived from polymorphonuclear leukocytes,
however.
SUMMARY AND CONCLUSIONS
Wounds of seven days' duration or less presented in gênerai two zones: (1) a
central zone of hemorrhage and necrosis and (2) a peripheral zone of edema and
perivascular hemorrhages. Degenerative changes predominated in both zones
but prolifération of endothelial cells of the capillaries and small blood vessels
became évident on the fourth day and was fairly well developed by the seventh
day. Between the seventh and the tenth day, the zone of edema had been transformed gradually into a zone of capillaries and proliferating endothelial cells
and fibroblasts. A third zone, consisting of hypertrophied astrocytes peripheral
to the zone of capillaries, also became apparent during this time. From the
twelfth day onward the process of organization continued and graduai absorption
of the necrotic débris in the central portion of the wound and its partial replacement by a network of capillaries and fibroblasts occurred. Numerous compound
granular corpuscles were présent between the capillaries and the reticular fibers.
After a month or two, fibroblastic prolifération subsided but connective tissue
fibrils were more numerous than before. Observations of wounds of six months'
duration or more indicated that the healing process had progressed very slowly
and that complète repair had not yet taken place. Observations of older wounds
suggest that complète closure of the defect may or may not take place, depending
on the extent of the original injury.
Compared with wounds in other parts of the body there is a decided lack of
vigor in the healing process of wounds of the brain and repair takes place at a
348
A. H. BAGGENSTOSS, J. W. KEBNOHAN AND J. F. DRAPIEWSKI
very slow tempo. Repair is more vigorous in the cortex than in the white matter, but no différence could be detected as between children and adults.
Astrocytes play a minor rôle in the reparative process and actual prolifération
and participation of thèse cells in the formation of a scar was not observed in
wounds of less than six months' duration.
Microglial cells appear to play only a very small rôle in the'production of
compound granular corpuscles. Most of the latter appear to hâve their origin
in the endothelial cells associated with capillaries, in the adventitial cells of
the larger blood vessels and in the mononuclear cells of the circulating blood.
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Verànderungen bei den traumatischenFormenderacutenEncephalitis.
Milnchen. med. Wchnschr., 33: 433,
1886.
(2) COEN, EDMONDO: Ueber die Heilung
von Stichwunden des Gehirnes.
Beitr. z. path. Anat. u. z. allg. Path.,
2: 107, 1888.
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