Summary
The density and distribution of brain damage after 2–10 min of cerebral ischemia was studied in the rat. Ischemia was produced by a combination of carotid clamping and hypotension, followed by 1 week recovery. The brains were perfusion-fixed with formaldehyde, embedded in paraffin, subserially sectioned, and stained with acid fuchsin/cresyl violet. The number of necrotic neurons in the cerebral cortex, hippocampus, and caudate nucleus was assessed by direct visual counting.
Somewhat unexpectedly, mild brain damage was observed in some animals already after 2 min, and more consistently after 4 min of ischemia. This damage affected CA4 and CA1 pyramids in the hippocampus, and neurons in the subiculum. Necrosis of neocortical cells began to appear after 4 min and CA3 hippocampal damage after 6 min of ischemia, while neurons in the caudoputamen were affected first after 8–10 min.
Selective neuronal necrosis of the cerebral cortex worsened into infarction after higher doses of insult. Damage was worst over the superolateral convexity of the hemisphere, in the middle laminae of the cerebral cortex. The caudate nucleus showed geographically demarcated zones of selective neuronal necrosis, damage to neurons in the dorsolateral portion showing an all-or-none pattern. Other structures involved included the amygdaloid, the thalamic reticular nucleus, the septal nuclei, the pars reticularis of the substantia nigra, and the cerebellar vermis.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Auer RN, T, Olsson Y, Siesjö BK (1984a) Hypoglycemic brain damage: Correlation of density of brain damage with the EEG isoelectric time. Diabetes (in press)
Auer RN, Wicloch T, Olsson Y, Siesjö BK (1984b) The distribution of hypoglycemic brain damage. Acta Neuropathol (Berl) 64:177–191
Ben-Ari Y, Dingledine R, Kanazawa I, Kelly JS (1976) Inhibitory effects of acetylcholine on neurones in the feline nucleus reticularis thalami. J Physiol 261:647–671
Blomqvist P, Mabe H, Ingvar M, Siesjö BK (1984) Models for studying long-term recovery following forebrain ischemia in the rat. I. Circulatory and functional effects of four-vessel occlusion. Acta Neurol Scand 69:376–384
Bowen D, Goodhart M, Strong A, Smith C, White P, Branston N, Symon L, Davison A (1976) Biochemical indices of brain structure, function and “hypoxia” in cortex from baboons with middle cerebral artery occlusion. Brain Res 117:503–507
Brown AW, Levy DE, Kublik M, Harrow J, Plum F, Brierley JB (1979) Selective chromatolysis of neurons in the gerbil brain: A possible consequence of “epileptic” activity produced by common carotid artery occlusion. Ann Neurol 5:127–138
DeGirolami U, Cromwell RM, Marcoux FW (1984) Selective necrosis and total necrosis in focal cerebral ischemia. Neuropathologic observations on experimental middle cerebral artery occlusion in the Macaque monkey. J Neuropathol Exp Neurol 43:57–71
Diemer NH, Siemkowicz E (1981) Regional neurone damage after cerebral ischemia in the normo- and hypoglycemic rat. Neuropathol Appl Neurobiol 7:217–227
Francis A, Pulsinelli W (1982) The response of GABAergic and cholinergic neurons to transient cerebral ischemia. Brain Res 243:271–278
Garcia JH, Kamijyo Y (1974) Cerebral infarction. Evolution of histopathologic changes after occlusion of a middle cerebral artery in primates. J Neuropathol Exp Neurol 33:408–421
Ginsberg MD, Budd WW, Welsh FA (1978) Diffuse cerebral ischemia in the cat. I. Local blood flow during severe ischemia and recirculation. Ann Neurol 3:482–492
Ginsberg MD, Graham DI, Welsh FA, Budd WW (1979) Diffuse cerebral ischemia in the cat. III. Neuropathologic sequelae of severe ischemia. Ann Neurol 5:350–358
Grenell RG (1964) Central nervous system resistance. I. The effects of temporary arrest of cerebral circulation for periods of two to ten minutes. J Neuropathol Exp Neurol 5:131–154
Hirsch H, Müller HA (1962) Funktionelle und histologische Veränderungen des Kaninchengehirns nach kompletter Gehirnischämie. Pflügers Arch 275:277–291
Harrison MJG, Arnold J, Sedal L, Ross Russel RW (1975) Ischaemic swelling of cerebral hemisphere in the gerbil. J Neurol Neurosurg Psychiatry 38:1194–1196
Houser CR, Vaughn JE, Barber RP, Roberts E (1980) GABA neurons are the major cell type of the nucleus reticularis thalami. Brain Res 200:341–354
Hudetz AG, Halsey JH, Jr, Horton CR, Conger KA, Reneau DD (1982) Mathematical simulation of cerebral blood flow in focal ischemia. Stroke 13:693–700
Ito U, Spatz M, Walker JT, Jr, Klatzo I (1975) Experimental cerebral ischemia in Mongolian gerbils. I. Light-microscopic observations. Acta Neuropathol (Berl) 32:209–223
Ito U, Ohno K, Nakamura R, Saganuma F, Inaba Y (1979) Brain edema during ischemia and after restoration of blood flow. Measurement of water, sodium, potassium content, and plasma protein permeability. Stroke 10:542–547
Ito U, Ohno K, Yamaguchi T, Tomita H, Inaba Y, Kashima M (1980) Transient apparance of “no-reflow” phenomenon in Mongolian gerbils. Stroke 11:517–521
Katzman R, Clasen R, Klatzo I, Mayer JS, Pappius HM, Waltz AG (1977) IV. Brain edema in stroke. Stroke 8:512–540
Kirino T (1982) Delaved neuronal death in the gerbil hippocampus following ischemia. Brain Res. 239:57–69
Kirino T, Sano K (1984a) Selective vulnerability in the gerbil hippocampus following transient ischemia. Acta Neuropathol (Berl) 62:201–208
Kirino T, Sano K (1984b) Fine structural nature of delayed neuronal death following ischemia in the gerbil hippocampus. 62:209–218
Kågström E, Smith M-L, Siesjö BK (1983a) Local cerebral flood flow in the recovery period following complete cerebal ischemia in the rat. J Cereb Blood Flow Metab 3:170–182
Kågström E, Smith M-L, Siesjö BK (1983b) Recirculation in the rat brain following incomplete ischemia. J Cereb Blood Flow Metab 3:183–192
Myers RE (1979) Lactic acid accumulation as a cause of brain edema and cerebral necrosis resulting from oxygen deprivation. In: Korobkin R, Guillemineault G (eds) Advances in perinatal neurology. Spectrum Publishers, New York, pp 85–114
Paxinos G, Watson C (1982) The rat brain in steotaxic coordinates. Academic Press, Sydney New York London Paris
Pulsinelli WA, Brierley JB (1979) A new model of bilateral hemispheric ischemia in the unanesthetized rat. Stroke 10:267–272
Pulsinelli WA, Brierley JB, Plum F (1982a) Temporal profile of neuronal damage in a model of transient forebrain ischemia. Ann Neurol 11:491–498
Pulsinelli WA, Levy DE, Duffy TE (1982b) Regional cerebral blood flow and glucose metabolism following transient forebrain ischemia. Ann Neurol 11:499–509
Sloper JJ, Johnson P, Powell TPS (1980) Selective degeneration of interneurons in the motor cortex of infant monkeys following controlled hypoxia: A possible cause of epilepsy. Brain Res 198:204–209
Smith M-L, Béndek G, Dahlgren N, Rosén I, Wieloch T, Siesjö BK (1984) Models for studying long, term recovery following forebrain ischemia in the rat. II. A two-vessel occlusion model. Acta Neurol Scand (in press)
Suzuki R, Yamaguchi T, Kirino T, Orzi F, Klatzo I (1983a) The effects of 5-min ischemia in Mongolian gerbits. I. Blood brain barrier, cerebral blood flow, and local cerebral glucose utilization changes. Acta Neuropathol (Berl) 60:207–216
Suzuki R, Yamaguchi T, Li C-L, Klatzo J (1983b) The effects of 5-min ischemia in Mongolian gerbils. II. Changes of spontaneous neuronal activity in the cerebral cortex and CA1 sector of the hippocampus. Acta Neuropathol (Berl) 60:217–222
White OB, Norris JW, Hachinski VC, Lewis A (1979) Death in early stroke, causes and mechanisms. Stroke 10:743
Author information
Authors and Affiliations
Additional information
Supported by the Swedish Medical Research Council (projects 12X-03020, 14X-263) and the National Institutes of Health of the United States Public Health Service (grant no. 5 R01 NS07838). Dr. Auer is the recipient of a Medical Research Council of Canada Fellowship.
Rights and permissions
About this article
Cite this article
Smith, M.L., Auer, R.N. & Siesjö, B.K. The density and distribution of ischemic brain injury in the rat following 2–10 min of forebrain ischemia. Acta Neuropathol 64, 319–332 (1984). https://doi.org/10.1007/BF00690397
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00690397