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PATOS Research Center

Pathophysiology and Treatment of Stroke

A functional blood-brain barrier (BBB) is required to maintain low brain extracellular K+ homeostasis, which can be crucial for recovery after stroke. Several studies have shown that specific brain-to-blood K+ transport mechanisms exist at the antiluminal surface of the BBB, functioning to keep brain ECF K+ constant and low. This suggests the importance of specific brain-to-blood K+ transport mechanisms at the site of the BBB that may be responsible for secretion of K+ from brain ECF into the blood. Additionally, nicotine has been shown to exert direct BBB permeability effects believed to be through the activation of nAChRs.

Experiments conducted in Dr. Abbruscato’s Laboratory directly related to this brain stroke research center have tested the effects of in vitro nicotine/cotinine or smoke condensate exposure on bovine brain microvessel endothelial cell (BBMEC) K+ uptake following hypoxia (Figure 1). Additionally, we have tested the effects of prior nicotine exposure (6 hours) on cerebral edema and infarct volume using a murine model of focal ischemia (MCAO) (Figure 2).

 

   
     
       

  Figure 1. In vitro stroke experiments clearly show that 1) hypoxia/aglycemia increases abluminal (brain facing) potassium uptake in bovine brain microvascular endothelial cell monolayers, 2) nicotine/cotinine and whole smoke condensate significantly decreases abluminal potassium uptake after six hour hypoxia/aglycemia, 3) denicotinized smoke condensates do not produce a significant decrease from six hours hypoxia/aglycemia. In the future, we plan to investigate the effects of hypoxia-reoxygentation to model the effects of establishing reperfusion after stroke.

     
   

         
           

Figure 2. (left) Exacerbation of cerebral edema (expressed as edema ratio) after 4.5 mg/kg nicotine injected intraperitoneally 6 hours minutes before MCAO; (right) exacerbation of infarct size (expressed as infarct ratio) in the same animals: both experiments were conducted 24 hours after MCAO (* denotes P<0.05 determined by Student’s t-test.

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