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

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.

Keywords: early brain injury; mouse model; neurocognitive function; neurotropin; subarachnoid hemorrhage.

Figure 1

Experimental protocol EP, endovascular perforation, to create SAH. NTP, neurotropin; OFT, open-field test.

Figure 2

Effects of neurotropin on newly developed cerebral infarction (A) and the Kaplan–Meier survival curve (B) in mice after-SAH. * p < 0.05; Fisher’s extract test. NTP, neurotropin.

Figure 3

Time–course changes of the cardiorespiratory and cerebrovascular parameters in the acute phase after SAH induction in the control and neurotropin groups. Body weight (A). Neuroscore (B). Total distance (C) and ratio of the central/total distance (D) obtained in the open-field test. * p < 0.05 vs. baseline; ^† p < 0.05 vs. control; two-way ANOVA with a post hoc analysis (Bonferroni–Dunn’s test). NTP, neurotropin.

Figure 4

Time–course changes in the acute phase after SAH induction in the control and neurotropin groups. Peak systolic flow velocity (PFV) of the right (A) and left (B) middle cerebral arteries (MCA). Cardiac output (CO) (C). Oxygen saturation (SpO₂) (D). * p < 0.05 vs. baseline; two-way ANOVA with a post hoc analysis (Bonferroni–Dunn’s test). NTP, neurotropin.

Figure 5

Time–course changes in the chronic phase after SAH induction in the control and neurotropin groups. Number of visited arms (A). Alternation index (B). * p < 0.05 vs. baseline; ^† p < 0.05 vs. control; two-way ANOVA with a post hoc analysis (Bonferroni–Dunn’s test). NTP, neurotropin.