| Summary: | 博士 === 國立陽明大學 === 生理學研究所 === 95 === 1. Although systemic cooling recently has been reported to be effective in improving the neurologic outcome after traumatic brain injury as well as heatstroke, several problems are associated with whole-body cooling.
In the first part of the present study, the effectiveness of brain cooling without interference with the core temperature in rats after fluid percussion traumatic brain injury (TBI) has been tested. Brain dialysates markers for ischemia (e.g., glutamate and lactate-to-pyruvate ratio) and injury (e.g., glycerol) before and after TBI were measured in rats with mild brain cooling (33 ℃), and the sham control group. Brain cooling was accomplished by infusion of 5 ml cold (4 ℃) saline via the external jugular vein under general anesthesia. The weight loss was determined by the difference between the first and third day of body weight after TBI. The maximal grip angle in an inclined plane was measured to determine motor performance whereas the percent of maximal possible effect was used to measure blockade of proprioception. The triphenyltetrazolium chloride staining procedure was used for cerebral infarction assay. As compared to those of the sham-operated controls, the animals with TBI had higher values of extracellular levels of glutamate, lactate-pyruvate ratio, and glycerol in brain and intracranial pressure, but lower values of cerebral perfusion pressure. Brain cooling adopted immediately after TBI significantly attenuated the TBI-induced increased cerebral ischemia and injury markers, intracranial hypertension, and cerebral hypoperfusion. In addition, the TBI-induced cerebral infarction, motor and proprioception deficits, and body weight loss evaluated 3 days after TBI were significantly attenuated by brain cooling. Experiments successfully demonstrate that brain cooling causes attenuation of TBI in rats by reducing cerebral ischemia and injury resulting from intracranial hypertension and cerebral hypoperfusion. Because jugular venipuncture is an easy procedure frequently used in the emergency department, for preservation of brain function, jugular infusion of cold saline may be useful in resuscitation for trauma patients.
2. In the second part of the current study, Experiments further assessed the effects of brain cooling on production of reactive nitrogen species, reactive oxygen species, tumor necrosis factor-α, and interleukin-10 in both serum and brain during heatstroke. Rats, under general anesthesia, were randomized into the following groups and given: a) 36 ℃ or b) 4 ℃ saline infusion in the external jugular vein immediately after onset of heatstroke. They were exposed to an ambient temperature of 43 ℃ for exactly 70 mins to induce heatstroke. When the 36 ℃ saline-treated rats underwent heat stress, their survival time values were found to be 21 to 25 min. Immediately after the onset of heatstroke, resuscitation with an i.v. dose of 4 ℃ saline greatly improved survival (226-268 min). Compared with the normothermic controls, the 36 ℃ saline-treated heatstroke rats displayed higher levels of brain temperature, intracranial pressure, serum and hypothalamic nitric oxide metabolite, tumor necrosis factor-α and dihydroxybenzoic acid as well as hypothalamic inducible nitric oxide synthase immunoreactivity. In contrast, the values of mean arterial pressure, cerebral perfusion pressure, and hypothalamic levels of local blood flow, and partial pressure of oxygen were all significantly lower during heatstroke. The cerebrovascular dysfunction, the increased levels of nitric oxide metabolites, tumor necrosis factor-α, and dihydroxybenzoic acid in both serum and the hypothalamus, and the increased levels of hypothalamic inducible nitric oxide synthase immunoreactivity occurring during heatstroke were significantly suppressed by brain cooling. Although, the serum and hypothalamic interleukin-10 maintained at negligible levels before stress, they were significantly elevated by brain cooling during heatstroke. These findings suggest that brain cooling may resuscitate rats who had a heatstroke by decreasing overproduction of reactive nitrogen species, tumor necrosis factor-α, reactive oxygen species and cerebrovascular dysfunction, but increasing production of interleukin-10.
3. The work reported here strongly indicates that the neurological outcome after traumatic brain injury as well as heatstrokes can be effectively suppressed by brain cooling caused by retrograde jugular vein cold saline flush.
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