Effects of topical N-methyl-D-aspartate on blood-brain barrier permeability in the cerebral cortex of normotensive and hypertensive rats

Abstract

This study was performed to examine if blood-brain barrier (BBB) permeability could be increased by N-methyl-D-aspartate (NMDA) in the cerebral cortex, and to compare the degree of alteration of BBB permeability in normotensive and iii chronic hypertensive rats. Twenty- to 22-week-old spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were anesthetized with isoflurane. After craniotomy in 7 animals in each group (SHR and WKY group), an NMOA patch (10 mM) was placed on one cortex (ipsilateral cortex: IC)I and a normal saline patch was placed on the other cortex (control cortex: IC). The other 7 rats in each group were pretreated with MK-801 before placing NMDA and normal saline patches (SHR MK-801 and WKY MK-801 group). The BBB transfer coefficient (ki) was determined using 14C-alpha-aminoisobutyric acid. The mean arterial pressures of the SHR and the SHR MK-801 group were about 65% higher than those of the WKYand the WKY MK-801 groups. In the WKY groupl the Ki of the IC was significantly higher than that of the CC (IC: 1O.O±2.71 CC: 6.2± 2.4 μl g-l min-l). In the WKY MK801 groupl the Ki was similar in both cortices (IC: 8.6± 4.01 CC: 8.2± 3.3). In the SHR groupl the Ki of the IC was significantly higher than that of the CC (IC: 9.5± 3.71 CC: 6.5± 3.4), and the Ki of each cortex was similar to that ofthe corresponding cortex ofthe WKY group. In the SHR MK-B01 groupl the Ki was similar in both cortices (IC: 7.2 ± 1.51 CC: 7.1 ± 2.7), and was also similar to those of the WKY MK-801 group. Our data suggest that NMOA is involved in increasing BBB permeability. In chronic hypertensionl the response of the BBB to NMOA is not altered when compared with normotension. [Neural Res 1997; 19: 539-544]