Endothelin receptors A and B are expressed in distinct cellular compartments of rat hippocampus following global ischemia: an immunocytochemical study.

OBJECTIVES: The syntheses of endothelin receptors A and B were previously shown to be upregulated in rat dorsal hippocampus after traumatic brain injury. Here we characterize endothelin receptor A and endothelin receptor B cellular distribution in hippocampus after permanent global brain ischemia and their possible association to nerve cell injury. METHODS: Twenty-minute global ischemia was induced using the Pulsinelli's four-vessel occlusion in conjunction with systemic hypovolemia in male rats. Endothelin receptor A and endothelin receptor B immunoreactivities from sham-operated and ischemic rats were assessed qualitatively in dentate gyrus, Cornu Ammonis, and hilus regions of the hippocampus. Quantitative immunoreactivity measurements were also obtained by optical densitometry. RESULTS: In sham-operated control hippocampus, endothelin receptor A immunoreactivity was absent in nerve cell bodies but strongly expressed in the mossy fiber pathway (axons of dentate gyrus granule cells). After ischemia endothelin receptor A immunoreactivity in the same regions was reduced by 40-50% from control. In contrast, endothelin receptor B immunoreactivity in control hippocampus was widely distributed in pyramidal neurons, granule cells and glial cells, this immunoreactivity increasing by approximately 25-30% after ischemia. DISCUSSION: Endothelin receptor A's marked decrease in mossy fibers after ischemia may contribute to glutamate release from mossy fiber terminals, thus enhancing excitotoxic effects on their Cornu Ammonis synaptic targets. Additionally, endothelin receptor B increased expression in neurons and glia could be related to a more generalized activation of survival mechanisms involving elements of the neurovascular unit.

Comparison of kinetic variables and muscle activity during a squat vs. a box squat.

The purpose of this investigation was to determine if there was a difference in kinetic variables and muscle activity when comparing a squat to a box squat. A box squat removes the stretch-shortening cycle component from the squat, and thus, the possible influence of the box squat on concentric phase performance is of interest. Eight resistance trained men (Height: 179.61 ± 13.43 cm; Body Mass: 107.65 ± 29.79 kg; Age: 24.77 ± 3.22 years; 1 repetition maximum [1RM]: 200.11 ± 58.91 kg) performed 1 repetition of squats and box squats using 60, 70, and 80% of their 1RM in a randomized fashion. Subjects completed the movement while standing on a force plate and with 2 linear position transducers attached to the bar. Force and velocity were used to calculate power. Peak force and peak power were determined from the force-time and power-time curves during the concentric phase of the lift. Muscle activity (electromyography) was recorded from the vastus lateralis, vastus medialis, biceps femoris, and longissimus. Results indicate that peak force and peak power are similar between the squat and box squat. However, during the 70% of 1RM trials, the squat resulted in a significantly lower peak force in comparison to the box squat (squat = 3,269 ± 573 N, box squat = 3,364 ± 575 N). In addition, during the 80% of 1RM trials, the squat resulted in significantly lower peak power in comparison to the box squat (squat = 2,050 ± 486 W, box squat = 2,197 ± 544 W). Muscle activity was generally higher during the squat in comparison to the box squat. In conclusion, minimal differences were observed in kinetic variables and muscle activity between the squat and box squat. Removing the stretch-shortening cycle during the squat (using a box) appears to have limited negative consequences on performance.

Differential effects of endothelin receptor A and B antagonism on cerebral hypoperfusion following traumatic brain injury.

OBJECTIVES: Our laboratory has previously shown that endothelin 1 (ET-1), a powerful vasoconstrictor, and its receptors, A (ETrA) and B (ETrB), are up-regulated following trauma. This up-regulation coincides temporally with enhanced vasoreactivity in cerebral cortical microvessels, which leads to a state of chronic hypoperfusion for up to 48 hours following traumatic brain injury (TBI). However, the direct contribution of either receptor up-regulation to decreased cerebral blood flow (CBF) after closed head trauma has not been determined. Furthermore, how ET-1 blockade may affect histological outcome following TBI has not been explored. Therefore, the effects of ETrA and B antagonism on TBI induced hypoperfusion of CBF and cell injury in sensorimotor cortex (smCx) and hippocampus (Hipp) were assessed by arterial spin labeling magnetic resonance imaging and Fluoro-Jade staining, respectively. METHODS: Adult male rats were given intracerebroventricular injections of ETrA (BQ123) or ETrB antagonist (BQ788) before being subjected to TBI using a closed head acceleration impact model. Following TBI, CBF was measured and histological examination of cell integrity was carried out. RESULTS: ETrA blockade ameliorated TBI induced hypoperfusion in smCx and Hipp at 4 and 24 hours after TBI and caused a mild hyperemia in both centers by 48 hours after injury. Furthermore, ETrA antagonism reduced the extent of Fluoro-Jade labeled cells within smCx and Hipp as compared with TBI only. ETrB blockade had little effect on TBI induced hypoperfusion and did not change the extent of cell injury following TBI. DISCUSSION: These results suggest that decreased CBF following TBI may be caused by ETrA, but not ETrB, up-regulation. Furthermore, these results suggest that TBI induced hypoperfusion may contribute to poor neurologic outcome following TBI. In this work, we provide a rationale for studying the clinical relevancy of use of ETrA antagonists following TBI.