The role of postischemic recirculation in the development of ischemic neuronal injury following complete cerebral ischemia

Abstract

The neuronal response to complete cerebral ischemia (CCI) of 5-15 min duration was evaluated at the light and electron microscopic level subsequent to postischemic recirculation periods of up to 60 min. Following postischemic reperfusion, the homogeneous neuronal changes characteristic of permanent CCI were modified into a heterogeneous pattern of selectively vulnerable neuronal responses. Four basic types of neuronal injury were represented within this heterogeneous neuronal population. The Type I neuronal response was most numerous and consisted of chromatin clumping, nucleolar condensation and a breakdown of polysomes. This response may represent a reversal of some of the neuronal changes observed after permanent CCI. In addition to the above changes, Type II neurons contained swollen mitochondria and Golgi saccules which appeared as microvacuoles under the light microscope. Type III neurons displayed varying degrees of neuronal shrinkage and numerous swollen mitochondria. Type IV neurons were markedly shrunken and electron-dense with few identifiable subcellular structures. The distribution of Type I neurons was random but the other neuronal responses occurred in "selectively vulnerable" brain regions. The number of Type II, III, and IV neurons increased with extended insult durations but were unaffected by the length of recirculation. Ten minutes of CCI represented the threshold for a significant increase in the number of severely altered neurons. These findings suggest that considerable neuronal injury may be present after 10-15 min of CCI, and the lack of a recirculation period following CCI appears to afford the brain parenchyma an extensive degree of structural protection.

Studies on Cerebral Protection of Digoxin against Ischemia/Reperfusion Injury in Mice

“…32,33) Cerebral ischemia has been reported to impair memory because hippocampal neurons are susceptible to the deleterious eŠects of ischaemia and reperfusion and hippocampus is involved in regulation of memory. 34) Cerebral ischemia is further documented to impair motor ability as well. 35) There- fore, in the present investigation we employed elevated plus maze test to assess memory and rota-rod test, inclined beam walk test and lateral push test for evaluation of motor coordination.…”

Pharmacologic analysis of the mechanism of dark neuron production in cerebral cortex

“…In perfusion-Wxed CNS tissue free of intravascular red blood cells, dark neurons have been shown in ischemia [2,15,19], hypoglycemia [1], epilepsy [26,29], electrical stimulation [13], exposure to excitatory amino acids [27], in addition to mechanical brain trauma. We conclude that neither local nor general brain trauma is a requirement for the production of dark neurons, despite the fact that dark neurons can be produced in mechanical brain injury [9,12].…”

Possible Involvement of Insulin, Endogenous Opioids and Calcitonin Gene Related Peptide in Remote Ischaemic Preconditioning of Brain

“…27,28) Cerebral ischaemia has been reported to impair short-term memory because hippocampal neurons are susceptible to the deleterious eŠects of ischaemia and reperfusion 29) and hippocampus is involved in regulation of short term memory. Cerebral ischaemia is further documented Fig.…”