Loss of white matter olieodendrocvtes and astrocytes in progressive"subcortici1 vascular encephalopathy of Binswanger tvge J
Yamanouchi H. Loss of white matter oligodendrocytes and astrocytes in progressive subcortical vascular encephalopathy of Binswanger type. Acta Neurol Scand 1991: 83: 301-305. To study whether oligodendrocytes and astrocytes can be affected in progressive subcortical vascular encephalopathy of Binswanger type (PSVE), the number of oligodendrocytes and astrocytes was counted in the white matter of frontal lobe. A sum of the number of oligodendrocytes and astrocytes in the deep white matter in PSVE accounted for approximately half of that in the age-matched controls. The number of oligodendrocytes, which were defined as the cells with small, round and solid nuclei in the present study, also decreased in PSVE showing half of that in the deep white matter of the controls. The present data suggest that the loss of oligodendrocytes and astrocytes can play a role to the process of nerve fibres loss in PSVE, which has been reported in my previous study (l), although the possibility that nerve fibres loss results in the secondary loss I of oligodendrocytes can not be ruled out.
From the electron microscopic study, I reported the loss of nerve fibres in the cerebral white matter in progressive subcortical vascular encephalopathy of Binswanger type (1). However, pathological process of the nerve fibres loss remains obscure, although that loss might be induced by cerebral ischemia based on severe atherosclerotic and/or arteriolosclerotic cerebral arteries (2-4), or by cerebral edema associated with or without ischemic conditions (5,6). The loss of nerve fibres in PSVE may result from a primary myelinopathy such as multiple sclerosis, or from an axonopathy including Wallerian degeneration, or from an oligodendropathy. The white matter pallor observed in PSVE seems too widespread to be induced only by the sum of Wallerian degeneration originated from multiple small infarctions, which were frequently associated with PSVE. Although it is not clear whether neurons in the cerebral cortex can be damaged in PSVE, the fact that U-fibres, which are situated between the cortex and the white matter, are usually preserved in PSVE (2,4) does not lend support to the possibility that neuronal damage in the cortex or lacunar infarctions in the white matter can be the main causes for the diffuse white matter pallor. Because if that mechanism might be main, the U-fibres could be also affected as well as deep white matter. Not only a primary myelinopathy but also an oligodendropathy can result in the nerve fibres loss. Oligodendrocytes may be sensitive and vulnerable
1
H. Yamanouchi Department of Neurology, Tokyo Metropolitan Geriatric Hospital, Japan
Key words: oligodendrocytes; astrocytes; white matter; progressive subcortical vascular encephalopathy; Binswanger; nerve fibres Hiroshi Yamanouchi, Department of Neurology, Tokyo Metropolitan Geriatric Hospital, 35-2 Sakaecho, Itabashiku, Tokyo-173, Japan Accepted for publication October 24, 1990
for the hypoperfusion or chronic edema in the cerebral white matter, which can be pathogenetic factors for the diffuse white matter change in PSVE (5-7). Next, it remains obscure whether the number of astrocytes increases or decreases as a whole in PSVE, although reactive astrocytes appeared sometimes surrounding the lacunes. To study whether oligodendrocytes and/or astrocytes can be affected in PSVE, I counted the number of oligodendrocytes and astrocytes in the frontal white matter of PSVE. Material and methods
From the autopsy series in Tokyo Metropolitan Geriatric Hospital, the number of oligodendrocytes and astrocytes was examined in 12 patients with PSVE, and in 12 age-matched control cases. Their pathology was confirmed on the light microscopic examination. Diagnosis of PSVE was based on the presence of diffuse pallor in the cerebral white matter on myelin staining associated with multiple small infarctions there (2). All of PSVE patients were demented. In the control cases, 10 died from cancer such as lung, colon, pancreas, and gastric cancer, one from multiple myeloma, and one from sudden death. All had no dementia. Single small lacunae were observed in the basal ganglia or the pons in 5 control cases, but cerebral white matter was well preserved in all cases. Age, sex and brain weight in each case were shown 301
Yamanouchi Table 1. Number of sum of oligodendrocytes and astrocytes, and of oligodendrocytes in the cerebral white matter in control cases At U-fibres/O.21 mm2
Under U-fibres/O.21 mm2
Deep white matter/0.21 mm2
Case No.
Age/ Sex
Brain weight
ODC and Astrocytes
ODC
ODC and Astrocytes
ODC
ODC and Astrocytes
ODC
1 2 3 4 5 6 7 8 9 10 11 12
69,F 76.M 76.F 80.M 80,M
lll0g 1330g 12309 1400 g 1480 g 1160 g 1050 g 14109 1250g 1510g 1220 g 1200 g
42 1 422 340 479 429 386 456 316 377 473 261 40 1
215 189 172 245 204 182 207 140 192 26 1 111 177
36 1 344 268 446 415 353 318 318 355 406 276 366
212 152 131 195 236 180 135 149 20 1 210 142 173
370 402 27 1 392 41 1 358 389 337 328 359 284 379
214 205 154 185 232 192 189 163 180 187 140 198
397 64
191 41
352 53
176 35
357 45
187 26
80,M 80,F 82,M 82,M 83,M 83,F 87,F
Mean value Standard deviation ODC: oligodendrocytes.
in Table 1 and 2. The mean age was 79.6 f 3.7 (standard deviation) years in PSVE, 79.8 f 4.5 years in the controls. The mean age was not different significantly between the two groups. The mean brain weight was 1193 f 126 (standard deviation) g in PSVE, 1279 2 147 gin the controls. The mean brain weight was not different significantly between the two groups. The time from death to autopsy varied from 2 to 29 hours with mean time of 13.9 8.1 (standard deviation) hours in PSVE, from 1 to 22 hours with mean time of 11.8 7.5 hours in the controls. The interval did not differ between the two groups. The duration of formalin fixation varied from 1 to 2
months, and it was not different significantly between the two groups. The number of oligodendrocytes and astrocytes was counted in the followingthree areas in the frontal lobe (Figure 1); a) An area of U-fibres at the bottom of cortical sulcus, in which nerve fibres were preserved relatively well in PSVE. b) An area under the U-fibres, which was pallor on myelin staining in PSVE. c) An area in the deep white matter, which was also pallor in PSVE. Measurements were performed using the Polaroid photographs of 400 magnifications in the 9 p width section stained with Kluver-Barrera method. Macrophages, microglia with oval or spindle-shaped
Table 2. Number of sum of oligodendrocytes and astrocytes, and of oligodendrocytes in the cerebral white matter in progressivesubcortical vascular encephalopathyof 8inswanger type At U-fibreslO.21 mm2
Under U-fibres/O.Zl mm2
Deep white matter/0.21 mm2
Case No.
Age/ Sex
Brain weight
ODC and Astrocytes
ODC
ODC and Astrocytes
ODC
ODC and Astrocytes
ODC
1
73,M 75,M 75,M 79,M 79.F 80,F 81,F 81,F 81,F 82,F 84,F 85,F
1210 g 1250 g 13409 1490 g 1130 g 1120g 1240 g 1050 g 1200g 1080 g 1090 g lll0g
304 382 29 1 375 478 35 1 256 35 1 315 361 274 299
152 244 148 195 229 20 1 131 147 165 155 161 137
247 264 259 279 325 298 194 293 182 232 258 263
118 163 149 129 134 171 120 123 96 96 155 151
167 226 190 151 186 225 167 210 145 186 202 219
85 142 102 81 110 135 94 96 71 88 111 132
336 60
172 37
258 41
134 25
190 28
104 23
2 3 4 5 6 7 8 9 10 11 12 Mean value Standard deviation
ODC: oligodendrocytes.
302
Loss of glial cells in PSI+ nuclei were counted as a sum of oligodendrocytes and astrocytes. Cells with small, solid and round nuclei were considered as the oligodendrocytes in the present study (Figure 2). In each case, the number of the cells was counted in 5 different visual fields selected at random of total area of 0.21 mm2. Statistical analysis was performed using Student’s t test. Results
Fig. 1. Oligodendrocytes and astrocytes were counted in the following three areas in the frontal lobe. A) Area of the U-fibres at the bottom of cortical sulcus. B) Area under the U-fibres. C) Area in the deep white matter.
nuclei, and vessel wall cells were excluded from the counting. All other cells with clear focussed round
The number of oligodendrocytes and astrocytes in each case was shown in Table 1 and2. The mean value of sum of oligodendrocytes and astrocytes in PSVE accounted for 85% of that in the controls at the U-fibres, 73 % of that in the area under U-fibres, and 53 % of that in the deep white matter. The mean value of sum of oligodendrocytes and astrocytes was significantly less in PSVE than in the age-matched controls (p < 0.05 at the U-fibres, p < 0.001 under the U-fibres and in the deep white matter, Figure 3). The mean number of oligodendrocytes in PSVE accounted for 90% Of that in the at the U-fibres, 76% of that in the area under U-fibres, and 56% of that in the deep white matter. The mean number of oligodendrocytes was significantly less in PSVE than that in the controls (p < 0.01 under the U-fibres, p < 0.001 in the deep white matter) except that at the U-fibres (Figure 4).
Fig. 2. Decrease in number of both oligodendrocytes and astrocytes in PSVE (B) compared with that in normal controls (A). Arrows show astrocytes, arrow heads show oligodendrocytes. Kliiver-Barrera stain. Polaroid (Type 667) photographs of 400 magnifications. PSVE: progressive subcortical vascular encephalopathy.
303
Yamanouchi
,
Number of sum of oligodendrocytes and astrocytes: 0.21mm:
Discussion
The present study indicated that a sum of oligodendrocytes and astrocytes decreased in its number in the frontal white matter in PSVE, and that the Control I I number of oligodendrocytes also decreased in PSVE except that at the U-fibres, in which nerve fibres were relatively well preserved even in PSVE (1,2). In the deep white matter, the number of these cells in PSVE b) Under U-fibres 0 ?ool accounted for approximately half of that in the agematched controls. Control The thickness of the sections would influence the cell counts. In the present study thickness of the PSVE sections might be not always constant strictly in each case, since the thickness of 9 p was measured by the c) Deepwhitematter 0 100 290 300 4po instrument attached to the microtome. Therefore, I Control I I counted only the cells with clear focussed nuclei, to reduce the error which might be induced by the thickPSVE f+** ness of each section. In the morphometric study of postmortem fixed * p
Yamanouchi H. Loss of white matter oligodendrocytes and astrocytes in progressive subcortical vascular encephalopathy of Binswanger type. Acta Neurol Scand 1991: 83: 301-305. To study whether oligodendrocytes and astrocytes can be affected in progressive subcortical vascular encephalopathy of Binswanger type (PSVE), the number of oligodendrocytes and astrocytes was counted in the white matter of frontal lobe. A sum of the number of oligodendrocytes and astrocytes in the deep white matter in PSVE accounted for approximately half of that in the age-matched controls. The number of oligodendrocytes, which were defined as the cells with small, round and solid nuclei in the present study, also decreased in PSVE showing half of that in the deep white matter of the controls. The present data suggest that the loss of oligodendrocytes and astrocytes can play a role to the process of nerve fibres loss in PSVE, which has been reported in my previous study (l), although the possibility that nerve fibres loss results in the secondary loss I of oligodendrocytes can not be ruled out.
From the electron microscopic study, I reported the loss of nerve fibres in the cerebral white matter in progressive subcortical vascular encephalopathy of Binswanger type (1). However, pathological process of the nerve fibres loss remains obscure, although that loss might be induced by cerebral ischemia based on severe atherosclerotic and/or arteriolosclerotic cerebral arteries (2-4), or by cerebral edema associated with or without ischemic conditions (5,6). The loss of nerve fibres in PSVE may result from a primary myelinopathy such as multiple sclerosis, or from an axonopathy including Wallerian degeneration, or from an oligodendropathy. The white matter pallor observed in PSVE seems too widespread to be induced only by the sum of Wallerian degeneration originated from multiple small infarctions, which were frequently associated with PSVE. Although it is not clear whether neurons in the cerebral cortex can be damaged in PSVE, the fact that U-fibres, which are situated between the cortex and the white matter, are usually preserved in PSVE (2,4) does not lend support to the possibility that neuronal damage in the cortex or lacunar infarctions in the white matter can be the main causes for the diffuse white matter pallor. Because if that mechanism might be main, the U-fibres could be also affected as well as deep white matter. Not only a primary myelinopathy but also an oligodendropathy can result in the nerve fibres loss. Oligodendrocytes may be sensitive and vulnerable
1
H. Yamanouchi Department of Neurology, Tokyo Metropolitan Geriatric Hospital, Japan
Key words: oligodendrocytes; astrocytes; white matter; progressive subcortical vascular encephalopathy; Binswanger; nerve fibres Hiroshi Yamanouchi, Department of Neurology, Tokyo Metropolitan Geriatric Hospital, 35-2 Sakaecho, Itabashiku, Tokyo-173, Japan Accepted for publication October 24, 1990
for the hypoperfusion or chronic edema in the cerebral white matter, which can be pathogenetic factors for the diffuse white matter change in PSVE (5-7). Next, it remains obscure whether the number of astrocytes increases or decreases as a whole in PSVE, although reactive astrocytes appeared sometimes surrounding the lacunes. To study whether oligodendrocytes and/or astrocytes can be affected in PSVE, I counted the number of oligodendrocytes and astrocytes in the frontal white matter of PSVE. Material and methods
From the autopsy series in Tokyo Metropolitan Geriatric Hospital, the number of oligodendrocytes and astrocytes was examined in 12 patients with PSVE, and in 12 age-matched control cases. Their pathology was confirmed on the light microscopic examination. Diagnosis of PSVE was based on the presence of diffuse pallor in the cerebral white matter on myelin staining associated with multiple small infarctions there (2). All of PSVE patients were demented. In the control cases, 10 died from cancer such as lung, colon, pancreas, and gastric cancer, one from multiple myeloma, and one from sudden death. All had no dementia. Single small lacunae were observed in the basal ganglia or the pons in 5 control cases, but cerebral white matter was well preserved in all cases. Age, sex and brain weight in each case were shown 301
Yamanouchi Table 1. Number of sum of oligodendrocytes and astrocytes, and of oligodendrocytes in the cerebral white matter in control cases At U-fibres/O.21 mm2
Under U-fibres/O.21 mm2
Deep white matter/0.21 mm2
Case No.
Age/ Sex
Brain weight
ODC and Astrocytes
ODC
ODC and Astrocytes
ODC
ODC and Astrocytes
ODC
1 2 3 4 5 6 7 8 9 10 11 12
69,F 76.M 76.F 80.M 80,M
lll0g 1330g 12309 1400 g 1480 g 1160 g 1050 g 14109 1250g 1510g 1220 g 1200 g
42 1 422 340 479 429 386 456 316 377 473 261 40 1
215 189 172 245 204 182 207 140 192 26 1 111 177
36 1 344 268 446 415 353 318 318 355 406 276 366
212 152 131 195 236 180 135 149 20 1 210 142 173
370 402 27 1 392 41 1 358 389 337 328 359 284 379
214 205 154 185 232 192 189 163 180 187 140 198
397 64
191 41
352 53
176 35
357 45
187 26
80,M 80,F 82,M 82,M 83,M 83,F 87,F
Mean value Standard deviation ODC: oligodendrocytes.
in Table 1 and 2. The mean age was 79.6 f 3.7 (standard deviation) years in PSVE, 79.8 f 4.5 years in the controls. The mean age was not different significantly between the two groups. The mean brain weight was 1193 f 126 (standard deviation) g in PSVE, 1279 2 147 gin the controls. The mean brain weight was not different significantly between the two groups. The time from death to autopsy varied from 2 to 29 hours with mean time of 13.9 8.1 (standard deviation) hours in PSVE, from 1 to 22 hours with mean time of 11.8 7.5 hours in the controls. The interval did not differ between the two groups. The duration of formalin fixation varied from 1 to 2
months, and it was not different significantly between the two groups. The number of oligodendrocytes and astrocytes was counted in the followingthree areas in the frontal lobe (Figure 1); a) An area of U-fibres at the bottom of cortical sulcus, in which nerve fibres were preserved relatively well in PSVE. b) An area under the U-fibres, which was pallor on myelin staining in PSVE. c) An area in the deep white matter, which was also pallor in PSVE. Measurements were performed using the Polaroid photographs of 400 magnifications in the 9 p width section stained with Kluver-Barrera method. Macrophages, microglia with oval or spindle-shaped
Table 2. Number of sum of oligodendrocytes and astrocytes, and of oligodendrocytes in the cerebral white matter in progressivesubcortical vascular encephalopathyof 8inswanger type At U-fibreslO.21 mm2
Under U-fibres/O.Zl mm2
Deep white matter/0.21 mm2
Case No.
Age/ Sex
Brain weight
ODC and Astrocytes
ODC
ODC and Astrocytes
ODC
ODC and Astrocytes
ODC
1
73,M 75,M 75,M 79,M 79.F 80,F 81,F 81,F 81,F 82,F 84,F 85,F
1210 g 1250 g 13409 1490 g 1130 g 1120g 1240 g 1050 g 1200g 1080 g 1090 g lll0g
304 382 29 1 375 478 35 1 256 35 1 315 361 274 299
152 244 148 195 229 20 1 131 147 165 155 161 137
247 264 259 279 325 298 194 293 182 232 258 263
118 163 149 129 134 171 120 123 96 96 155 151
167 226 190 151 186 225 167 210 145 186 202 219
85 142 102 81 110 135 94 96 71 88 111 132
336 60
172 37
258 41
134 25
190 28
104 23
2 3 4 5 6 7 8 9 10 11 12 Mean value Standard deviation
ODC: oligodendrocytes.
302
Loss of glial cells in PSI+ nuclei were counted as a sum of oligodendrocytes and astrocytes. Cells with small, solid and round nuclei were considered as the oligodendrocytes in the present study (Figure 2). In each case, the number of the cells was counted in 5 different visual fields selected at random of total area of 0.21 mm2. Statistical analysis was performed using Student’s t test. Results
Fig. 1. Oligodendrocytes and astrocytes were counted in the following three areas in the frontal lobe. A) Area of the U-fibres at the bottom of cortical sulcus. B) Area under the U-fibres. C) Area in the deep white matter.
nuclei, and vessel wall cells were excluded from the counting. All other cells with clear focussed round
The number of oligodendrocytes and astrocytes in each case was shown in Table 1 and2. The mean value of sum of oligodendrocytes and astrocytes in PSVE accounted for 85% of that in the controls at the U-fibres, 73 % of that in the area under U-fibres, and 53 % of that in the deep white matter. The mean value of sum of oligodendrocytes and astrocytes was significantly less in PSVE than in the age-matched controls (p < 0.05 at the U-fibres, p < 0.001 under the U-fibres and in the deep white matter, Figure 3). The mean number of oligodendrocytes in PSVE accounted for 90% Of that in the at the U-fibres, 76% of that in the area under U-fibres, and 56% of that in the deep white matter. The mean number of oligodendrocytes was significantly less in PSVE than that in the controls (p < 0.01 under the U-fibres, p < 0.001 in the deep white matter) except that at the U-fibres (Figure 4).
Fig. 2. Decrease in number of both oligodendrocytes and astrocytes in PSVE (B) compared with that in normal controls (A). Arrows show astrocytes, arrow heads show oligodendrocytes. Kliiver-Barrera stain. Polaroid (Type 667) photographs of 400 magnifications. PSVE: progressive subcortical vascular encephalopathy.
303
Yamanouchi
,
Number of sum of oligodendrocytes and astrocytes: 0.21mm:
Discussion
The present study indicated that a sum of oligodendrocytes and astrocytes decreased in its number in the frontal white matter in PSVE, and that the Control I I number of oligodendrocytes also decreased in PSVE except that at the U-fibres, in which nerve fibres were relatively well preserved even in PSVE (1,2). In the deep white matter, the number of these cells in PSVE b) Under U-fibres 0 ?ool accounted for approximately half of that in the agematched controls. Control The thickness of the sections would influence the cell counts. In the present study thickness of the PSVE sections might be not always constant strictly in each case, since the thickness of 9 p was measured by the c) Deepwhitematter 0 100 290 300 4po instrument attached to the microtome. Therefore, I Control I I counted only the cells with clear focussed nuclei, to reduce the error which might be induced by the thickPSVE f+** ness of each section. In the morphometric study of postmortem fixed * p
