Minimally Invasive Surgery for Intracerebral Hematoma Evacuation followed by Rosiglitazone Infusion Therapy Increased Perihematomal Occludin, Zonula Occludens-1 Expression and Decreased the Blood Brain Barrier Permeability in Rabbits

Abstract

Objective: To observe the effects of minimally invasive surgery (MIS) for hematoma of intracerebral hemorrhage (ICH) evacuation followed by rosiglitazone (RSG) infusion therapy on perihematomal tight junction associated proteins occludin and zonula occludens-1 (ZO-1) expression as well as blood brain barrier (BBB) permeability in rabbits.Methods: A total of 50 male rabbits (2.5-3.5 kg) were randomly assigned to a sham group (Sham group, 10 rabbits), an ICH model group (HM group, 10 rabbits), a RSG medication group (RSG group, 10 rabbits), a minimally invasive surgery group (MIS group, 10 rabbits) and a MIS combined with RSG group (MIS+RSG group, 10 rabbits). ICH was induced in all of the rabbits except for those in the Sham group. An MIS was performed to evacuate the hematoma at 6 hours after the successful preparation of the ICH model in the MIS group and the MIS+RSG group. The RSG (0.5mg, dissolved in 0.1 ml of 0.9% sodium chloride solution) was infused into the hematoma area in the RSG group and the MIS+RSG group. All rabbits were sacrificed on day 7 after the relative processes were performed successfully, and the perihematomal brain tissue was removed to determine the occludin and ZO-1 expression and BBB permeability by Evens Blue (EB). Results:The occludin and ZO-1 expression were all significantly decreased and the BBB permeability was increased in the HM group compared with the Sham group. The RSG used alone or performing the MIS alone to evacuate the ICH resulted in a marked increase in the occludin and ZO-1 expression and decrease in BBB permeability. The MIS+RSG group displayed a great increase in the occludin and ZO-1 expression and a more significant decrease in BBB permeability. Conclusions:The MIS combined with RSG medication could significantly increase the perihematomal occludin and ZO-1 expression and decrease in BBB permeability which plays an important therapeutic role in secondary brain damage following ICH. KeywordsIntracerebral hemorrhage, Minimally invasive surgery, Rosiglitazone, Tight junction, Occludin, Zonula occludens-1, Blood-brain barrier Rosiglitazone (RSG), an agonist of peroxisome proliferator-activated receptor-gamma (PPARγ), has shown neuroprotective effects in patients with ischemic stroke and Alzheimer's disease. It has reported that RSG could significantly reduce brain tissue loss, ameliorated white matter injury, and improved sensorimotor and cognitive functions and increased the numbers of newly generated mature oligodendrocytes after middle cerebral artery occlusion [24]. RSG reversed depressive behaviors in mice, as indicated by the forced swimming test and open field test. RSG was also found to inhibit the inflammatory response, decrease corticosterone levels, promote astrocyte proliferation and neuronal axon plasticity in the prefrontal cortex of mice, and exerts an antidepressive effect in unpredictable chronic mildstress-induced depressive mice by maintaining essential neuron autophagy and inhibiting excessive astrocytic apoptosis [25]. Several studies have ...