Abstract
External ventricular drain (EVD) is used clinically to relieve intracranial pressure and occasionally to deliver medications following intracerebral hemorrhage (ICH). Mesenchymal stem cell (MSC) therapy has been shown to be neuroprotective and can induce neuroregeneration in stroke models. We evaluated the safety and efficacy of delivering MSCs intraventricularly in a rat hemorrhagic stroke model. Using autologous blood, hemorrhagic stroke was induced at specific coordinates in the right basal ganglia. After 30 minutes, rats were treated with either bone marrow-derived MSCs or a phosphate-buffered saline placebo via direct intraventricular infusion. Three dosages (2 × 105/kg, 5 × 105/kg, and 1 × 106/kg) of MSCs were administered. Forelimb use asymmetry test was employed to evaluate functional improvement after cell therapy. At the end of the experiment, peripheral blood samples and organs were harvested; biochemistry, cytokine, and growth factor analysis and histology evaluations were performed to explore cell toxicity and cell fate, and the effects of MSC therapy on injury volume, anti-inflammation, and neurogenesis. Intraventricular administration of MSCs in ICH rat model showed improved behavior and alleviated brain damage. Additionally, treated ICH rats showed significantly reduced expression of IL-1α, IL-6, and IFN-γ. No obvious cell toxicity was noticed through blood chemistry and histology evaluation. None of the infused MSCs were detected at the end of the experiment. EVD is safe and effective to use as a method of delivering MSCs to treat ICH. Intraventricularly delivered MSCs have anti-inflammatory properties and a capacity to induce neurogenesis and improve function following ICH injury.
Highlights
Using an external ventricular drain (EVD) is one of the most common lifesaving procedures used in neurologic intensive care units
hematoxylin and eosin (H&E) slides from brain, heart, liver, lung, spleen, testis and kidney organ tissues showed no evidence of therapy-related cytopathic changes
Spontaneous intracerebral hemorrhage (ICH) can extend into the cerebrospinal fluid cavities causing intraventricular hemorrhage (IVH), which leads to increased intracranial pressure (ICP), decreased cerebral perfusion pressure, and potentially global brain ischemia unless there is an intervention
Summary
Using an external ventricular drain (EVD) is one of the most common lifesaving procedures used in neurologic intensive care units. MSC therapy appears to be a promising cell-based therapy, with proven safety and some efficacy in animal models and in clinical trials[8,9,10]. MSCs are known to be immunosuppressive, and can control inflammatory response following ICH. Several studies have demonstrated the effectiveness of MSCs in cerebral hypoxia-ischemia models[12,13,14,15,16]. To our knowledge, no study has evaluated MSC administration via EVD in a hemorrhagic stroke model or assessed the feasibility of using EVD catheter to deliver therapeutic MSC in a clinical trial. We assessed the safety and therapeutic effect of intraventricularly administered BM-MSCs in an ICH rat model
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