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Abstract
Intracerebral hemorrhage (ICH) is a critical disease, highly associated with mortality and morbidity. Several studies have demonstrated the beneficial effect of mesenchymal stem cells (MSCs) on ICH, mostly focused on their mid-to-long-term effect. Acute hematoma expansion is one of the most important prognostic factors of ICH. We hypothesized that MSCs would decrease mortality and hematoma size in acute ICH, based on the findings of a few recent researches reporting their effect on blood-brain barrier and endothelial integrity. Rat ICH models were made using bacterial collagenase. One hour after ICH induction, the rats were randomly divided into MSC-treated and control groups. Mortality, hematoma volume, ventricular enlargement, brain edema, and degenerating neuron count were compared at 24 hours after ICH induction. Expression of tight junction proteins (ZO-1, occludin) and coagulation factor VII mRNA was also compared. Mortality rate (50% versus 8.3%), hematoma size, ventricular size, hemispheric enlargement, and degenerating neuron count were significantly lower in the MSC-treated group (p = 0.034, 0.038, 0.001, 0.022, and <0.001, resp.), while the expression of ZO-1 and occludin was higher (p = 0.007 and 0.012). Administration of MSCs may prevent hematoma expansion in the hyperacute stage of ICH and decrease acute mortality by enhancing the endothelial integrity of cerebral vasculature.
Highlights
Nontraumatic intracerebral hemorrhage (ICH) is highly associated with mortality and morbidity, with a substantially worse prognosis than ischemic stroke [1, 2]
Seven rats in the vehicle-treated group and eight rats in the mesenchymal stem cells (MSCs)-treated group were included in the histologic analyses, and three rats in each group were enrolled for Western blot and real-time polymerase chain reaction (PCR) (Figure 1(e))
To assess whether the reduction in mortality rate in the MSC-treated group correlated with reduced hematoma size, we examined the hematoma size at 24 hours following ICH
Summary
Nontraumatic intracerebral hemorrhage (ICH) is highly associated with mortality and morbidity, with a substantially worse prognosis than ischemic stroke [1, 2]. Though various therapeutic approaches to overcome the extremely poor prognosis of ICH have been studied, including the administration of neuroprotective agents and exogenous coagulation factors, only symptomatic treatments are currently considered effective therapeutic options for ICH [2, 6, 7]. Various medical therapies to overcome poor prognosis due to hematoma expansion, including the administration of corticosteroids, glycerol, and mannitol, have been studied, but none of these have shown beneficial effects in clinical trials [12,13,14].
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