PubMed · 10534870
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T Larner. 1999. Key developments in urology.. https://pubmed.ncbi.nlm.nih.gov/10534870/
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Brimonidine, a selective alpha(2)-adrenoceptor agonist, has recently been shown to be neuroprotective as it significantly improves survival of retinal ganglion cells (RGCs) after calibrated optic nerve injury in rats. In the present study, we examined the effect of brimonidine (alpha(2)-adrenoceptor agonist) on RGC survival after increased intraocular pressure (IOP) in adult rats. RGCs were prelabeled by bilateral tectal injection of 5% Fluoro-Gold (FG). Two days later, unilaterally IOP was increased 2.2-2.5 times (28-30.5 mmHg) that of the normal pressure (12.5-14.5 mmHg) by cauterization of three episcleral veins. The elevated IOP was maintained throughout the duration of the experiment. Rats were treated intraperitoneally with brimonidine (1 mg/kg) or phosphate-buffered saline (PBS) once per week beginning either before (group A) or after (group B) increasing the IOP. Another group of rats was left as the control with elevated IOP but without any brimonidine/PBS treatment. Rats were euthanized at 3, 4 and 5 weeks after IOP elevation. Identifiable RGCs were counted and compared between control and experimental groups. Brimonidine significantly protected RGCs from elevated IOP-induced cell death. In control rats with three-vein cauterization, there was 5-6% cell death per week. Almost all RGCs were protected following brimonidine treatment for 3 weeks both in groups A and B. At 4 weeks, there was 4.5% cell death in group A and 6.5% in group B. At 5 weeks, cell death was 5.9% in group A and 6.2% in group B. The difference in cell death in groups A and B was insignificant. No significant differences were observed between PBS-treated and control groups. No significant changes in elevated IOP was found after brimonidine or PBS treatment when compared with the nontreated control group. Although pressure remained elevated throughout the length of the experiment, 3 weeks later the amount of cell death gradually increased in brimonidine-treated animals.
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Electrical stimulation of the lateral hypothalamus (LH) produces antinociception partially blocked by intrathecal alpha-adrenergic antagonists, but the mechanism underlying this effect is not clear. Evidence from immunological studies demonstrates that substance P-immunoreactive neurons in the LH project near the A7 catecholamine cell group, a group of noradrenergic neurons in the pons known to effect antinociception in the spinal cord dorsal horn. Such evidence suggests that LH neurons may activate A7 neurons to produce antinociception. To test this hypothesis, the cholinergic agonist carbachol was microinjected into the LH at doses of 63, 125 and 250 nmol and the resulting effects on tail-flick and nociceptive foot-withdrawal latencies were measured. All three doses significantly increased response latencies on both tests, with the 125-nmol dose providing the optimal effect. Intrathecal injection of the opioid antagonist naltrexone (97 nmol) partially reversed antinociception, but neither the alpha(2)-adrenoceptor antagonist yohimbine nor the alpha(1)-adrenoceptor antagonist WB4101 altered latencies. However, two sequential doses of yohimbine blocked LH-induced antinociception on both tests. In contrast, two sequential doses of WB4101 increased nociceptive responses on both the tail-flick and foot-withdrawal tests. These findings, and those of published reports, suggest that neurons in the LH activate spinally projecting methionine enkephalin neurons, as well as two populations of A7 noradrenergic neurons that exert a bidirectional effect on nociception. One of these populations increases nociception through the action of alpha(1)-adrenoceptors and the other inhibits nociception through the action of alpha(2)-adrenoceptors in the spinal cord dorsal horn.