Role of astrocytes and gap junctions in seizure-induced pial arteriolar dilations in rats

Abstract

Cerebral arterioles and astrocytes are physically and physiologically linked to one another. Indeed, astrocyte-related factors appear to make a significant contribution to the local regulation of CBF. For example, in recent studies we reported that topical application of L-alpha-aminoadipic acid (L-AAA), an astroglial toxin which selectively damaged the glia limitans (without affecting vascular smooth muscle, endothelium, or neurons), was associated with a reduced pial arteriolar reactivity to selected vasodilating stimuli (e.g., hypercapnia and ADP; but not acetylcholine or NO). In the present study, we examined whether the pial arteriolar dilation accompanying seizure (topical bicuculline [BC]) was influenced by L-AAA-induced glial injury. In addition, we tested whether gap junctions influence the vascular response. These experiments employed topical applications of the gap junction inhibitory peptide, gap 27. To ensure that changes in the vasodilatory magnitude were not related to reduced brain activity, the local EEG activity (total EEG power) was monitored. We used anesthetized rats, with closed cranial windows inserted 24 h prior to study. L-AAA (or aCSF, 300 ul each) was introduced into the periarachnoid space immediately after window placement. BC (100 uM) was suffused over 15 min and pial arteriolar diameters measured every minute. Arteriolar responses in L-AAA- and aCSF-treated rats were compared. To assess gap junction contributions, the rats were exposed to two BC exposures (separated by 2 h). Gap 27 was topically applied for 1 h prior to the 2nd evaluation. In controls, the gap 27 was omitted. No differences in the magnitude of the EEG power increase were observed when comparing L-AAA or gap 27-treated rats to their controls. The arteriolar responses are summarized in the figure 1. The 20-25% increase in diameter that is normally seen during seizure was completely lost in L-AAA-treated rats. Topical blockade of gap junctions was associated with a 50% reduction in pial arteriolar dilation. These results indicate that astrocytes, and, to a lesser extent, gap junctions, contribute greatly to the cerebrovasodilation accompanying seizure.