Temporal Profile of Astrocytes and Changes of Oligodendrocyte-Based Myelin Following Middle Cerebral Artery Occlusion in Diabetic and Non-diabetic Rats

Abstract

The long-term impacts of cerebral ischemia and diabetic ischemia on astrocytes and oligodendrocytes have not been defined. The objective of this study is to define profile of astrocyte and changes of myelin in diabetic and non-diabetic rats subjected to focal ischemia.Focal cerebral ischemia of 30-min duration was induced in streptozotocin-induced diabetic and vehicle-injected normoglycemic rats. The brains were harvested for immunohistochemistry of glial fibrillary acidic protein (GFAP) and 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) at various reperfusion endpoints ranging from 30 min up to 28 days. The results showed that activate astrocytes were observed after 30 min and peaked at 3 h to 1 day after reperfusion in ischemic penumbra, and peaked at 7 days of reperfusion in ischemic core. Diabetes inhibited the activation of astrocytes in ischemic hemisphere. Demyelination occurred after 30 min of reperfusion in ischemic core and peaked at 1 day. Diabetes caused more severe demyelination compared with non-diabetic rats. Remyelination started at 7 days and completed at 14 and 28 days in ischemic region. Diabetes inhibited the remyelination processes. It is concluded that ischemia activates astrocytes and induces demyelination. Diabetes inhibits the activation of astrocytes, exacerbates the demyelination and delays the remyelination processes. These may contribute to the detrimental effects of hyperglycemia on ischemic brain damage.

Subcortical ischemic vascular disease: Roles of oligodendrocyte function in experimental models of subcortical white-matter injury

“…50 Furthermore, diabetes animals exacerbate the demyelination and delays the remyelination processes. 51 Cell-cell interaction between oligodendrocytes and other cells…”

Blood–Brain Barrier Disruption, Vascular Impairment, and Ischemia/Reperfusion Damage in Diabetic Stroke

“…Ischemic injury to the brain activates astrocytes, and reactive astrocytes can exert a deleterious role (secrete proinflammatory cytokines, inhibit axonal regeneration, infarct expansion) in the acute phase after stroke while exerting a protective role (neurite sprouting, synapse formation, rebuild BBB, secrete neurotrophic factors) in the chronic phase after stroke 50, 51. Using a model of forebrain ischemia in rats, it has been reported that diabetic hyperglycemia suppresses ischemia‐induced astrocyte activation, increases astrocyte cell death, damages the astrocyte end‐foot lining around cerebral vessels, and the damaged astrocytes exhibit increased withdrawal of the astrocyte end‐foot from the cerebral vessel wall 52, 53. Astrocytic end‐feet continuously line all cerebral blood vessels and the water channel protein Aquaporin‐4 is highly localized to astrocyte end‐feet 47.…”

“…DM decreases neuronal dendrite outgrowth and neuronal cell survival and increases cell death of myelin‐producing oligodendrocytes 9. In the diabetic brain, ischemia induces significant white matter rarefaction, decreases axon and myelin density, and decreases the proliferation and survival of oligodendrocytes progenitor cells, and delays remyelination 53, 79, 80, 81. Loss of myelin and axon density hinders the conduction of nerve signals and interneuronal communications affecting sensorimotor functions 76.…”

Neurochemical and behavioral processes in gerontogenesis in conditions of experimental hyperglycemia.

“…Са-управління при ЦД включає в себе такі види поведінки, як прийом медикаментів, контроль рівня глюкози в крові, виконання вправ, до-тримання відповідних дієтичних рекомендацій, догляд за ногами та регулярне відвідування лікаря [18,22]. У дослідженнях, де використовувалися методи нейровізуалізації, показано наявність структурних змін у головному мозку в пацієнтів з ЦД [39]. При проведенні магнітно-резонансної томографії встановлено зв'язок між ЦД і безсимптомними інфарктами мозку [23,39].…”