Intracerebral hirudin injection alleviates cognitive impairment and oxidative stress and promotes hippocampal neurogenesis in rats subjected to cerebral ischemia
Research article published in Neuropathology : official journal of the Japanese Society of Neuropathology (2023)
Abstract
Cerebral ischemia starts with cerebral blood flow interruption that causes severely limited oxygen and glucose supply, eliciting a cascade of pathological events, such as excitotoxicity, oxidative stress, calcium dysregulation, and inflammatory response, which could ultimately result in neuronal death. Hirudin has beneficial effects in ischemic stroke and possesses antioxidant and anti-inflammatory properties. Therefore, we investigated the biological functions of hirudin and its related mechanisms in cerebral ischemia. The ischemia-like conditions were induced by transient middle cerebral artery occlusion (MCAO). To investigate hirudin roles, intracerebroventricular injection of 10 U hirudin was given to the rats. Cognitive and motor functions were examined by beam walking and Morris water maze tests. 2,3,5-triphenyl tetrazolium chloride-stained brain sections were used to measure infarct volume. Oxidative stress was determined by assessment of oxidative stress markers. The proliferated cells were labeled by BrdU and Nestin double staining. Western blotting was performed to measure protein levels. Hirudin administration improved cognitive and motor deficits post-ischemia. Hirudin reduced brain infarction and neurological damage in MCAO-subjected rats. Hirudin alleviated oxidative stress and enhanced neurogenesis in ischemic rats. Hirudin facilitated the promotion of phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and serine-threonine kinase. In sum, hirudin alleviates cognitive deficits by attenuating oxidative stress and promoting hippocampal neurogenesis through the regulation of ERK1/2 and serine-threonine kinase in MCAO-subjected rats.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Summary
Cerebral ischemia starts with cerebral blood flow interruption that causes severely limited oxygen and glucose supply, eliciting a cascade of pathological events, such as excitotoxicity, oxidative stress, calcium dysregulation, and inflammatory response, which could ultimately result in neuronal death.
Why This Matters for Hirudotherapy
This study investigated whether intracerebroventricular hirudin injection (10 U) could improve cognitive and motor function, reduce brain infarct volume, attenuate oxidative stress, and promote hippocampal neurogenesis in rats subjected to transient middle cerebral artery occlusion (MCAO). As hirudin is the bioactive anticoagulant most closely associated with medicinal leeches and hirudotherapy, its demonstrated neuroprotective and neurogenic effects in a stroke model are of conceptual interest to the ASH domain. The abstract reports that hirudin improved behavioral outcomes, reduced infarct size, alleviated oxidative stress, and enhanced neurogenesis via ERK1/2 and serine-threonine kinase phosphorylation. However, this is a preclinical animal study using direct brain injection of purified hirudin — it involved no leeches and no leech therapy, and its relevance to clinical hirudotherapy is indirect and limited.
Citation
Intracerebral hirudin injection alleviates cognitive impairment and oxidative stress and promotes hippocampal neurogenesis in rats subjected to cerebral ischemia.
Xia X et al. · Neuropathology : official journal of the Japanese Society of Neuropathology, 2023
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