Neuronal injuries in cerebral infarction and ischemic stroke: From mechanisms to treatment (Review)

Abstract

Stroke is the leading cause of disabilities and cognitive deficits, accounting for 5.2% of all mortalities worldwide. Transient or permanent occlusion of cerebral vessels leads to ischemic strokes, which constitutes the majority of strokes. Ischemic strokes induce brain infarcts, along with cerebral tissue death and focal neuronal damage. The infarct size and neurological severity after ischemic stroke episodes depends on the time period since occurrence, the severity of ischemia, systemic blood pressure, vein systems and location of infarcts, amongst others. Ischemic stroke is a complex disease, and neuronal injuries after ischemic strokes have been the focus of current studies. The present review will provide a basic pathological background of ischemic stroke and cerebral infarcts. Moreover, the major mechanisms underlying ischemic stroke and neuronal injuries are summarized. This review will also briefly summarize some representative clinical trials and up‑to‑date treatments that have been applied to stroke and brain infarcts.

Keywords: cerebral infarcts; clinical management; ischemic stroke; mechanism; neuronal injury.

Figure 1

Kv2.1/Kv2.2 pathway in neuron protection. Kv, voltage-gated K⁺ channel. CREB, Cyclic AMP response-element binding protein; PI3K/Akt, phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B.

Figure 2

NMDARs mediate bidirectional regulation of neuronal survival or death. NMDAR, N-methyl-D-aspartate receptor; mGluR1, metabotropic glutamate receptor subtype 1; INSIG1, insulin-induced gene 1; SREBP1, sterol regulatory element binding protein 1; STEP, striatal-enriched protein tyrosine phosphatase; ERK, extracellular signal-regulated kinase; MAPK, mitogen-activated protein kinase; JNK, c-Jun N-terminal kinase; NCX3, sodium-calcium exchanger 3.

Figure 3

NMDARs induce neural toxicity through the GluN2B-postsynaptic density protein 95-nNOS axis. NMDAR, N-methyl-D-aspartate receptor; GluN2B, NMDAR receptor 2B; nNOS, neuronal nitric oxides synthase; PDZ, PSD95 discs-large and zona occludens-1; Tat-NR2B9c, postsynaptic density 95 blocking peptide; ZL006, a small-molecular inhibitor of the nNOS-PSD-95 interaction; SH3, Src Homology 3; GK, guanylate kinase.