Dexmedetomidine ameliorates intracerebral hemorrhage-induced memory impairment by inhibiting apoptosis and enhancing brain-derived neurotrophic factor expression in the rat hippocampus

Abstract

Intracerebral hemorrhage (ICH) is a severe type of stroke causing neurological dysfunction with a high mortality rate. Dexmedetomidine is an agonist for α2‑adrenoreceptors with sedative, anxiolytic, analgesic and anesthetic effects. In the present study, we investigated the effects of dexmedetomidine on short‑term and spatial learning memory, as well as its effects on apoptosis following the induction of ICH in rats. A rat model of IHC was created by an injection of collagenase into the hippocampus using a stereotaxic instrument. Dexmedetomidine was administered intraperitoneally daily for 14 consecutive days, commencing 1 day after the induction of ICH. The step‑down avoidance test for short‑term memory and the radial 8‑arm maze test for spatial learning memory were conducted. Terminal deoxynucleotidyl transferase‑mediated dUTP nick end-labeling (TUNEL) assay, immunohistochemistry for caspase‑3, and western blot analysis for Bcl‑2, Bax, Bid and caspase-3 expression were performed for the detection of apoptosis in the hippocampus. Western blot analysis for the brain‑derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) was also performed for the detection of cell survival in the hippocampus. The induction of ICH deteriorated short‑term and spatial learning memory, increased apoptosis and suppressed BDNF and TrkB expression in the hippocampus. Treatment with dexmedetomidine ameliorated the ICH‑induced impairment of short‑term and spatial learning memory by suppressing apoptosis and enhancing BDNF and TrkB expression. In the normal rats, dexmedetomidine exerted no significant effects on memory function and apoptosis. The present results suggest the possibility that dexmedetomidine may be used as a therapeutic agent for the conservation of memory function in stroke patients.

Retracted: MicroRNA‐140‐5p elevates cerebral protection of dexmedetomidine against hypoxic–ischaemic brain damage via the Wnt/β‐catenin signalling pathway

“…DEX has also been demonstrated to protect the brain against isoflurane‐induced neuroapoptosis in the hippocampus of neonatal rats by suppressing the p38MAPK signalling pathway 40. However, the side effects of DEX have also been indicated that DEX infusion results in mild analgesia, reversible sedation and memory impairment which may decrease central nervous system activity 41. So, DEX added with miR‐140‐5p mimic serves as a better treatment regimen than DEX infusion alone.…”

Voluntary wheel running ameliorates symptoms of MK-801-induced schizophrenia in mice

“…Decreased BDNF expression has been identified in several mental disorders, including schizophrenia and depression (26,38). Furthermore, induction of intracerebral hemorrhage has been demonstrated to suppress BDNF expression in the hippocampus, with the impairment in spatial learning memory occurring as a result (39). In the present study, repeated injections of the NMDA receptor antagonist MK-801 suppressed BDNF expression in the hippocampus.…”

Paeoniflorin attenuates hippocampal damage in a rat model of vascular dementia

“…Bcl-2 and Bax are two primary genes responsible for the regulation of apoptotic cell death, and their individual products possess opposing functions (24). Bcl-2 is functionally characterized as the apoptosis-suppressing factor, whereas Bax is considered as the apoptosis-promoting factor (25). Bcl-2 inhibits cytochrome c release from mitochondria elicited by the pro-apoptotic molecule Bax, resulting in the inhibition of caspase activation and apoptotic death (26,27).…”