Effects of hyperbaric oxygen on skin blood flow and tissue morphology following sciatic nerve constriction.

BACKGROUND: Constriction of the sciatic nerve by loose ligation produces an inflammatory neuropathic injury. This represents an animal model for peripheral mononeuropathy. Oxygen-derived free radicals are suspected to play an important role in the pathogenesis of ischemia/reperfusion injury, leading to neurogenic inflammation. Hyperbaric oxygen (HBO) has been used anecdotally to treat clinically similar conditions in humans, but specific effects on the animal model have not been well studied. OBJECTIVE: This study in a rat model examined the effects of hyperbaric oxygen on skin blood flow and tissue morphology by light and electron microscopy following sciatic nerve constriction. DESIGN: A scientific investigation in a rat model. METHODS: In this study, the neuropathic injury was established by loose ligation of the rat sciatic nerve. The animals were divided into three groups, sham (S, n=8), ligation but no treatment (LN, n=8) and ligation and treatment with hyperbaric oxygen (LT, n=8). The treatment group (n=8) received hyperbaric oxygen treatment immediately following the injury and daily for four additional days at the same time interval. One hundred percent O2 at 3 atmospheres absolute pressure (66 feet sea water) was administered for two hours. The hindpaws of the rats were observed by light microscopy, electron microscopy, laser Doppler flowmetry (LDF), and clinically for the presence of edema. RESULTS: Untreated animals demonstrated marked tissue edema following sciatic constriction, whereas animals that received hyperbaric oxygen had minimal to no edema. The sham group demonstrated normal histology. The group not treated with hyperbaric oxygen demonstrated swollen mitochondria (2-3 times), with loss of cellular integrity, multiple vacuole formation in both nerve and muscle tissue, widened sarcomeres in muscle, and degenerative changes in the nerve myelin sheaths. The group treated with hyperbaric oxygen demonstrated preservation of cellular structure including mitochondrial integrity, no vacuole formation, and maintenance of normal, easily identifiable nerve structure. The sham group had no change of skin blood flow. Skin blood flow of LT group was decreased immediately after ligation (p<0.05) and recovered to baseline level before ligation on Day 5 after four hyperbaric oxygen treatments. Skin blood flow of LN group was decreased immediately after ligation (p <0.01) and did not recover (p <0.01). CONCLUSION: This study evaluated tissue changes after nerve injury caused by loose ligation of the sciatic nerve in rats. Hyperbaric oxygen treatment following sciatic nerve injury reduced tissue edema, improved skin blood flow, and preserved muscle and neuronal ultrastructural integrity.

Comparison of three rat models of cerebral vasospasm.

A substantial number of rat models have been used to research subarachnoid hemorrhage-induced cerebral vasospasm; however, controversy exists regarding which method of selection is appropriate for this species. This study was designed to provide extensive information about the three most popular subarachnoid hemorrhage rat models: the endovascular puncture model, the single-hemorrhage model, and the double-hemorrhage model. In this study, the basilar artery and posterior communicating artery were chosen for histopathological examination and morphometric analysis. Both the endovascular puncture model and single-hemorrhage model developed significant degrees of vasospasm, which were less severe when compared with the double-hemorrhage model. The endovascular puncture model and double-hemorrhage model both developed more vasospasms in the posterior communicating artery than in the basilar artery. The endovascular puncture model has a markedly high mortality rate and high variability in bleeding volume. Overall, the present study showed that the double-hemorrhage model in rats is a more suitable tool with which to investigate mechanism and therapeutic approaches because it accurately correlates with the time courses for vasospasm in humans.

Morphological changes of cerebral arteries in a canine double hemorrhage model.

Cerebral vasospasm is a major cause of morbidity and mortality in patients suffering from subarachnoid hemorrhage (SAH). Despite numerous studies, the pathogenesis of this deadly disorder is not clearly understood. Alterations in endothelial cells are a distinct morphological feature of cerebral vasospasm and some recent studies suggest that apoptosis might play a role in the cells' death. The goal of the present study is to examine the time course of apoptosis in endothelial cells of spastic cerebral arteries following experimental subarachnoid hemorrhage. Fifteen dogs were used in the present study. Twelve of them were divided into three groups (four per group) and subjected to a double-hemorrhage method of SAH. Following SAH, groups were sacrificed respectively on days 3, 5, and 7. Three dogs served as controls without blood injection. The basilar arteries were studied with the transmission electron microscopy and with angiography. Angiographic vasospasm began on day 3 and peaked on day 7. In morphologic studies, control dogs did not demonstrate apoptotic-like changes in endothelial cells of the basilar arteries. Beginning with day 3, apoptotic-like changes were noted in endothelial cells and consisted of condensation of peripheral nuclear chromatin, blebbing of the cell membrane, and condensation of the cytoplasm. Such changes progressed with time and were maximally developed by day 7. This is the first study that demonstrates the time course of apoptotic-like changes in the endothelial cells in the vasospastic basilar artery. Apoptosis might play an important role in the pathogenesis of vasospasm.