Chung-Lung Cho

Injury severity and cell death mechanisms: effects of concomitant hypovolemic hypotension on spinal cord ischemia-reperfusion in rats.

A number of previous studies indicated that ischemia-reperfusion injury causes two distinct types of cell death--necrosis and apoptosis--in the central nervous system. It was also implicated that the intensity of injury can somehow affect the cell death mechanisms. By occluding the descending thoracic aorta with or without simultaneously induced hypovolemic hypotension in rats, we established a model of experimental spinal cord ischemia-reperfusion (I/R) in which the injury severity can be controlled. Recordings of carotid blood pressure (CBP) and spinal cord blood flow (SCBF) showed that aortic occlusion induced dramatic CBP elevation but SCBF drop in both the normotensive (NT) and hypotensive (HT) groups of rats. However, the HT group demonstrated significantly lower SCBF during aortic occlusion, and much slower elevation of SCBF after reperfusion, and extremely poor neurological performance. Spinal cord lesions were characterized by infarction associated with extensive necrotic cell death, but little apoptosis and caspase-3 activity. In contrast, in the NT group, I/R injury resulted in minor tissue destruction associated with persistent abundant apoptosis, augmented caspase-3 activity, and favorable functional outcome. The relative sparing of motoneurons in the ventral horns from apoptosis might have accounted for the minor functional impairment in the NT group. The severity of I/R injury was found to have substantial impact on the histopathological changes and cell death mechanisms, which correlate with neurological performance. Our results implicate that injury severity and duration after injury are two critical factors to be considered in therapeutic intervention.

Patterns of palmar skin temperature alterations during transthoracic endoscopic T2 sympathectomy for palmar hyperhidrosis.

Transthoracic endoscopic T2 sympathectomy has been widely applied to the treatment of a variety of sympathetically mediated disorders. Palmar hyperhidrosis is probably the most common indication for thoracic sympathectomy, especially in certain subtropical areas. Which sympathetic ganglion is to be ablated and how extensive such ablation is enough to eliminate palm sweating are two important issues. Intraoperative monitoring of palmar skin temperature (PST) is the most frequently used method for assessing the accuracy as well as adequacy of ablation of the target sympathetic ganglia. With continuous monitoring of bilateral PST during the operative course of T2 sympathectomy, it was possible to depict the alterations of bilateral PST in response to specific surgical procedures in a real-time manner. For each case, a PST graph was obtained, which represented the graphical expression of intraoperatively recorded bilateral PST data plotted against time. The PST graphs of 93 consecutive cases were analysed. Three types of PST graphs existed, reflecting different responses of bilateral PST to different surgical procedures during the operation. In Type I PST graph pattern, found in 58 cases, skin incision and intercostal muscle dissection caused dramatic bilateral PST drop; and unilateral T2 sympathectomy induced synchronous bilateral PST elevation. Twenty-four cases demonstrated Type II PST graph pattern, in which unilateral T2 sympathectomy caused only ipsilateral PST elevation, although the PST-depressing effect of skin incision and muscle dissection was as significant as in Type I graph pattern. In the 11 cases who showed Type III PST graph pattern, neither skin incision nor T2 sympathectomy induced any apparent changes of PST on either side, giving rise to two rather flat PST curves on the PST graphs. These findings implicate that reciprocal interactions between bilateral sympathetic activities exist in the majority of cases, and that crossover sympathetic modulation may play a role in the neural control of the sudomotor and vasomotor activities of the palms. This study also provides information regarding how PST would possibly change following specific surgical procedures during transthoracic endoscopic T2 sympathectomy, which may be of importance to those who use intraoperative PST monitoring as a guide in determining whether or not the correct sympathetic ganglia are ablated for adequate sympathetic denervation of the palms.

Simvastatin Combined with Antioxidant Attenuates the Cerebral Vascular Endothelial Inflammatory Response in a Rat Traumatic Brain Injury

Traumatic brain injury (TBI) leads to important and deleterious neuroinflammation, as evidenced by indicators such as edema, cytokine production, induction of nitric oxide synthase, and leukocyte infiltration. After TBI, cerebral vascular endothelial cells play a crucial role in the pathogenesis of inflammation. In our previous study, we proved that simvastatin could attenuate cerebral vascular endothelial inflammatory response in a rat traumatic brain injury. This purpose of this study was to determine whether simvastatin combined with an antioxidant could produce the same effect or greater and to examine affected surrogate biomarkers for the neuroinflammation after traumatic brain injury in rat. In our study, cortical contusions were induced, and the effect of acute and continuous treatment of simvastatin and vitamin C on behavior and inflammation in adult rats following experimental TBI was evaluated. The results demonstrated that simvastatin combined with an antioxidant could provide neuroprotection and it may be attributed to a dampening of cerebral vascular endothelial inflammatory response.

Neuroprotective synergy of N-methyl-D-aspartate receptor antagonist (MK801) and protein synthesis inhibitor (cycloheximide) on spinal cord ischemia-reperfusion injury in rats

Thoraco-abdominal aortic surgery requiring temporal cross clamping of the aorta results in a high incidence of paraplegia due to temporary ischemia of the spinal cord. Both excitotoxicity and apoptosis are implicated in the pathogenesis of spinal cord ischemia-reperfusion injury. We propose that the N-methyl-D-aspartate receptor antagonist dizocilpine maleate (MK801) and the protein synthesis inhibitor cycloheximide produce a synergic effect in a rodent model of spinal cord ischemia-reperfusion injury. Injury was induced by 20 min of temporal thoracic aorta occlusion and distal blood volume reduction. After injury, the animals were treated with vehicle, MK801, cycloheximide or MK801 and cycloheximide. Hind limb motor function recovery was better in the MK801 and combined therapy groups than in the control and cycloheximide groups. The mean neuronal survival rate of the control group was 45.3 +/- 3.2% on the 7(th) day after injury. In the MK801 and cycloheximide treatment groups, neuronal survival increased to 62.4 +/- 3.6% and 54.1 +/- 2.4%, respectively. For the combined therapy group, neuronal survival increased to 75.6 +/- 2.5%. The number of apoptotic cells in the control group was 211.4 +/- 8.8 per section on the 7th day after ischemic insult, while apoptosis was significantly reduced in the cycloheximide (96.8 +/- 6.7 cells) and combined (84.8 +/- 8.5 cells) groups. It was unchanged in the MK801 group (209.8 +/- 5.4 cells). These results suggest that combined treatments directed at blocking both N-methyl-D-aspartate receptor-mediated excitotoxic necrosis and caspase-mediated apoptosis might have synergic therapeutic potential in reducing spinal cord ischemia-reperfusion injury.

Delayed neurovascular inflammation after mild traumatic brain injury in rats.

Introduction: Experimental traumatic brain injury (TBI) elicits acute local inflammatory responses, including up-regulation of adhesion molecules and neutrophils in the injured brain. However, in clinical experiences there were at least three types of TBI, which included mild, moderate and severe types, and there would be different neuroinflammatory responses. This study investigated the inflammatory responses after mild TBI in rats. Methods: Adult male Sprague–Dawley rats (n = 40) were group-housed and injured using an impact method. Motor function was assessed 1–4 days after the injury by using a grip test (Grip strength meter; Singa). Blood samples collected from the rats before the injury and after the injury and the Intercellular adhesion molecule-1 (ICAM-1) level were measured. Results: The ICAM-1 expression from pre-injury to post-injury showed a significantly greater gradual elevation in the rats in the mild-injury group than in the moderate-injury group. The neurological function evaluated with grip test showed no deterioration of neurological function in the mild-injury group but gradual deterioration in the moderate-injury group. Conclusion: These findings showed a delayed inflammatory reaction in the mild-injury group without progressive deterioration of neurological function. Therefore, in the moderate-injury group, no progression phase was observed.

Molecular Biomarker of Inflammatory Response Is Associated with Rebleeding in Spontaneous Intracerebral Hemorrhage

Background and Purpose: Rebleeding in spontaneous intracerebral hemorrhage (ICH) is a major cause of morbidity and mortality among stroke survivors. Due to the links between inflammation and rebleeding, we hypothesized that the biomarkers of inflammation are associated with the pathogenesis of rebleeding in ICH. We sought to investigate whether these biomarkers and clinical variables on admission can provide prognostic information on the risk of rebleeding. Methods: This prospective study enrolled 59 consecutive patients with spontaneous ICH. We determined the concentrations of interleukin-10 (IL-10), intercellular adhesion molecule-1, and complement 3 in blood samples obtained on admission. Results: Univariate analysis indicated that hematoma volume, leukocyte count, hydrocephalus, and plasma IL-10 levels were associated with rebleeding. Multivariate logistic regression analysis indicated that hydrocephalus (95% CI of OR, 1.6–26.7) and IL-10 (95% CI of OR, 1.03–1.22) were independently associated with an increased probability of rebleeding. Conclusion: These data suggest that IL-10, a molecular biomarker of inflammatory response in the early acute phase of ICH, is associated with subsequent rebleeding.