Reduction of traumatic brain injury-induced cerebral oedema by a free radical scavenger

doi:10.1016/0014-2999(96)00235-X

European Journal of Pharmacology

Volume 307, Issue 2, 27 June 1996, Pages 149-155

https://doi.org/10.1016/0014-2999(96)00235-X Get rights and content

Abstract

Oxygen derived free radicals have been proposed to be in part responsible for the cerebral oedema resulting from head injury. In the present study the effects of free radical suppression with MDL 74, 180 (2,3-dihydro-2,2,4,6,7-pentamethyl-3-(4-methylpiperazino)-methyl-1-benzofuran-5-ol dihydrochloride), an α-tocopherol analogue free radical scavenger, on the development of cerebral oedema resulting from head injury has been assessed. Fluid percussion head injury in rats caused a regional oedema 48 h after injury. Infusion of MDL 74,180 for 2 h after the injury significantly attenuated oedema development in a dose-related manner. Using magnetic resonance imaging, cerebral oedema development was monitored in head injured mice. Oedema was apparent 4 h after head injury and was greatest in the vicinity of the olfactory bulb and surrounding the ventricles. Treatment with MDL 74,180 (1–10 μg/kg intravenously, administered 3–5 min after the injury) significantly reduced the oedema development. MDL 74,180 is a potential treatment for the oedema caused as a result of head injury.

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Citation Excerpt :
Sham-operated rats were treated exactly the same in all respects except that no impact was applied to the exposed dura. Mcintosh et al. [9,10] showed that a pressure greater than 253.3 kPa causes SHI. According to the formula, relating triggered pressure (P0) to actual pressure (P), P = 0.4476P0 − 47.144; the actual pressure we used was up to 257.2 kP.
The absorptive capacity of the gut is decreased after severe head injury (SHI), and this may be related to poor recovery. Probiotics may be a promising approach to improving gut absorption. The aim of this study was to investigate the effect of probiotics on gut absorptive capacity (GAC) after SHI.
A rat model in which SHI was induced by air percussion was used. One hundred fourteen Sprague-Dawley rats were randomized into three groups: SHI followed by standard enteral nutrition (group A); SHI followed by standard enteral nutrition plus probiotics (group B); and standard chow diet ad libitum (group C, sham-operated). The enteral diets were infused for 14 d after SHI.
SHI induced weight loss and decreased the serum concentration of D-xylose and the apparent protein digestibility. Probiotics significantly improved GAC after SHI. Apparent protein digestibility and the concentration of D-xylose were lower in group A than in B or C after 14 d. The rats receiving probiotics showed less weight loss than group A. SHI induced intestinal flora dysfunction and a decrease in villus height and surface area. Digestive enzyme activities and gut motion were also depressed significantly, and these changes were closely related to the decrease in GAC. Probiotics increased villus height and surface area; Escherichia coli counts decreased significantly, and anaerobic counts increased.
Probiotics improve the GAC after SHI, perhaps because of enhanced villus surface area, and correction of intestinal flora dysfunction.
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Le traumatisme crânien induit des lésions primaires et secondaires. Les lésions primaires résultent directement de la transmission d'énergie à l'encéphale et sont définitives. À l'inverse, les lésions secondaires sont progressives et se prolongent pendant plusieurs mois ou années dans des régions sélectivement vulnérables. Le rôle délétère de la neuro-inflammation initiale dans le développement des lésions de la barrière hématoencéphalique, de l'œdème cérébral, de la nécrose cellulaire et de l'apoptose est bien établi. Pour cette raison, après l'échec de la cible glutamatergique, une des approches dans la recherche de stratégies thérapeutiques permettant l'amélioration du pronostic des patients traumatisés crâniens graves s'est orientée vers la modulation de la réaction inflammatoire post-traumatique en s'intéressant entre autres à la voie du monoxyde d'azote aux cytokines pro-inflammatoires et au stress oxydant.
Traumatic brain injury leads to primary and secondary brain injuries. Primary brain injury results from mechanical forces applied to the head at the time of impact. Secondary brain injury occurs at some time after the primary impact. Numerous pathophysiological mechanisms have been postulated to explain the progressive tissue damage produced by secondary injuries. The endogenous neuroinflammatory response after traumatic brain injury contributes to the development of blood-brain barrier breakdown, cerebral oedema and neuronal cell death and this has led to various pharmacological therapies to try to limit this type of damage. Studies employing glutamate receptor antagonist for cerebral protection have yielded promising results in laboratory animals but failed to produce clinically significant improvements. The present review will summarize the mechanisms of post traumatic cerebral inflammation with a special focus on the anti-inflammatory drug targets.
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Reduction of traumatic brain injury-induced cerebral oedema by a free radical scavenger

Abstract

Eur J. Pharmscol.

Neurosci Lett.

Lipid hydrolysis and peroxidation in injured spinal cord: Partial protection with methylprednisolone or vitamin E and selenium

J. Neurotrauma

Protective effects of liposome-entrapped superoxide dismutase on posttraumatic brain oedema

Ann. Neurol.

Effect of D1 α-tocopheryl succinate and polyethyleneglycol on performance tests after fluid percussion injury

J. Neurotrauma

A fluid percussion model of experimental brain injury in the rat

J. Neurosurg.

Cyclooxygenase products of arachidonic acid metabolism in cat cerebral cortex after experimental concussive head injury

J. Neurochem.

Restoration of cerebrovascular responsiveness to hyperventilation by the oxygen radical scavenger n-acetylcysteine following experimental traumatic brain injury

J. Neuresurg.

2,3-Dihydro-1-benzofuran-5-ols as analogues of α-tocopherol that inhibit in vitro and ex vivo brain lipid autoxidation and protect mice against central nervous system trauma

J. Med. Chem.

High dose glucocorticoid treatment improves neurological recovery in head injured mice

J. Neurosurg

Comparison of two ester pro-drugs of methyl prednisolone on early neurologic recovery in a murine closed head injury model

J. Neurotrauma.

Effects of the 21-amino steroid U-74006F on experimental head injury in mice

J. Neurosurg.

Brain hydroxyl radical generation in acute experimental head injury

J. Neurochem

Oxygen-free radicals in traumatic brain oedema

Neurol. Res.

Effect of D₁ α-tocopheryl succinate and polyethyleneglycol on performance tests after fluid percussion injury