Neuroplastic Changes in Rat Hippocampus after Ischemic Stroke in the Neocortex: The Involvement of the Hypothalamic-Pituitary-Adrenal Axis System and the Neurotrophin System

Abstract—Middle cerebral artery occlusion (MCAO) is the cause of most ischemic strokes, resulting in focal brain damage affecting not only various cortical regions but also brain areas outside the infarction area, including the hippocampus. Activation of the hypothalamic-pituitary-adrenal axis (HPAA) leading to an increase in the circulating level of glucocorticoids, is one of the body’s first responses to cerebral stroke. The balance between the degree of HPAA activation and the neuroprotective potential of the neurotrophin system may determine the severity of remote damage to the hippocampus, a brain region with an extremely high density of corticosteroid receptors. In this work, we studied the dynamics of changes in the level of corticosterone, BDNF, and NGF in the blood and hippocampal regions of rats after transient MCAO. An increase in the level of corticosterone in the blood occurred in the early stages after MCAO and was accompanied by the presence of the stress hormone in the dorsal hippocampus (DH) of the ischemic hemisphere. In contrast to the unchanged level of circulating BDNF, the expression of this neurotrophin increased in the DH and ventral hippocampus (VH) during the early stages of reperfusion, whereas the level of NGF increased in the blood and afterwards only in the DH. Thus, ischemic stroke in the neocortex induces HPAA activation, corticosterone accumulation, and an increase in BDNF protein expression to a greater extent than NGF in the ipsilateral hippocampal regions at the early stages after MCAO.