Post-Event Application of Neurotropin Protects against Ischemic Insult toward Better Outcomes in a Murine Model of Subarachnoid Hemorrhage

Tatsushi Mutoh,Shuzo Yamamoto,Takahiro Moriya

doi:10.3390/biomedicines9060664

Tatsushi Mutoh, Shuzo Yamamoto + Show 1 more

Open Access

https://doi.org/10.3390/biomedicines9060664

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Abstract

Early brain injury (EBI) is closely linked to the development of delayed cerebral ischemia and poor outcomes after aneurysmal subarachnoid hemorrhage (SAH). This study aimed to evaluate the neuroprotective effect of neurotropin on EBI in a murine model of SAH. Twenty-four C57BL/6N mice were treated with intraperitoneal injections of either saline or 2.4 units of neurotropin at 1 h after SAH induction and for 3 days consecutively. SAH was created by an endovascular perforation method. In addition to the assessment of cerebral infarction and survival rate, motor and neurocognitive functions were also measured after SAH. Compared to the saline control group, the neurotropin group showed better recovery from locomotive and neurological declines after SAH. The neurotropin group also showed lower rates of post-SAH acute cerebral infarction and better memory and route-learning scores (p < 0.05). Meanwhile, there was no significant between-group differences in the overall mortality, hemodynamic parameters, or body weights. In conclusion, post-event treatment with neurotropin could be protective against EBI, lowering the incidence of ischemia and improving some motor and neurocognitive functions after SAH.

Highlights

Subarachnoid hemorrhage (SAH) is the leading cause of acute death and permanent disability in people with stroke worldwide [1]
Clinical and laboratory investigations have shown that early brain injury (EBI) is closely linked to poor outcomes and the development of delayed cerebral ischemia after SAH [2,3]
Laboratory investigations have shown that a 3-week oral intake of neurotropin prior to focal cerebral ischemia leads to reduced cerebral infarction and edema and improved neurological outcomes in a mouse model of temporary ischemic stroke [11]

Summary

Introduction

Subarachnoid hemorrhage (SAH) is the leading cause of acute death and permanent disability in people with stroke worldwide [1]. Clinical and laboratory investigations have shown that early brain injury (EBI) is closely linked to poor outcomes and the development of delayed cerebral ischemia after SAH [2,3]. Neurotropin is a nonprotein extract derived from the inflamed skin of rabbits inoculated with the vaccinia virus As it contains multiple physiologically active substances such as amino acids and nucleotides (e.g., ethanolamine, ornithine, uracil, and xanthine) [5], neurotropin is widely used in medical practices for treating chronic pain and allergies in. Laboratory investigations have shown that a 3-week oral intake of neurotropin prior to focal cerebral ischemia leads to reduced cerebral infarction and edema and improved neurological outcomes in a mouse model of temporary ischemic stroke [11]. Neurotropin upregulated the brain-derived neurotropic factor (BDNF) levels in the cerebral

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