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.