Aşkın Görgülü

Reduction of edema and infarction by Memantine and MK-801 after focal cerebral ischaemia and reperfusion in rat.

Summary N-methyl-D-aspartate (NMDA) receptor antagonists have been found to be protective after cerebral ischemia. However most of these drugs have limited value as neuroprotectives in clinical therapy because of their side effects. Memantine is a noncompetitive NMDA receptor antagonist and it has been used for the treatment of various cerebral disorders with relatively few side effects. We investigated the beneficial effects of Memantine and compared its effect with MK-801 in a temporary focal cerebral ischemia model. As cerebral ischemia model three hours middle cerebral artery occlusion (MCAO) with intraluminal thread and three hours reperfusion was used. 78 male Spraque-Dawley rats were divided into three groups as follows: Control (Saline), treatment 1 (MK-801), and treatment 2 (Memantine) groups. In the treated groups, 15 minutes after MCAO, MK-801 and Memantine were administered in amounts of 1 mg/kg and 10 mg/kg intraperitoneally respectively. After a 3 hour period of reperfusion, the animals were examined for neurological deficits and then killed. The following values were measured; cerebral water content, blood brain barrier (BBB) permeability at the core and periphery of the ischemic hemisphere and contralateral hemisphere and infarct volumes. The severity of neurological deficit (p<0.001) and infarct volume (p<0.001) was reduced in both Memantine and MK-801 treated groups compared with saline treated groups. Memantine attenuated brain edema formation and BBB permeability at the periphery (p<0.01), MK-801 both at the core (p<0.05) and the periphery (p<0.01) of the ischemia. These results demonstrated that the NMDA receptor antagonists Memantine and MK-801 were neuroprotective when given 15 min after MCAO in temporary focal cerebral ischemia.

The effects of memantine on lipid peroxidation following closed-head trauma in rats.

Memantine is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist. Unlike other NMDA antagonists, it has been used clinically for years for the treatment of Parkinson’s disease, spasticity, and dementia without serious side effects. We aimed to investigate the therapeutic efficacy of memantine on a closed head trauma model. A total of 132 adult male Sprague–Dawley rats were randomly divided into four groups: sham-operated, control (closed head trauma), sham-vehicle (closed head trauma + saline), treatment (closed head trauma + memantine, 10 mg/kg, i.p.). A cranial impact was delivered to the skull, just in front of the coronal suture, over the left hemisphere, from the height of 7 cm. Saline or memantine were applied 15 min after trauma. Rats were euthanased 0.5, 1, 2, 6, 24, 48 h after trauma. Brain tissue samples were taken 5 mm away from the left frontal pole and also from the corresponding point of the contralateral hemispheres. Malondialdehyde activity (MDA) was considered to reflect the degree of lipid peroxidation. The MDA levels continued to increase for the first 2 h after the injury, then started to decrease gradually. Memantine treatment significantly reduced lipid peroxidation levels in the treatment group compared with other groups (P<0.01). The findings of the present study indicate that memantine provides beneficial effects after closed head trauma in rats.

The Effect of Aprotinin on Extraneural Scarring in Peripheral Nerve Surgery: An Experimental Study

Summary Extraneural scarring is one of the factors negatively influencing the result of peripheral nerve surgery. Many organic materials have been used to prevent fibrosis. The effect of aprotinin on peripheral nerve scarring in rats was investigated in this study. Three types of surgical intervention were carried out; namely external neurolysis (I), abrasive injury (II), and anastomosis (III). The coded samples which consisted of pure collagen fibers soaked with aprotinin or phosphate-buffered saline were applied around the left sciatic nerves of rats whereas only sham operations were performed on the right sciatic nerves. Animals were sacrificed after 4 or 6 weeks. Neurological examination, gross evaluation of extraneural fibrosis, and histological study were undertaken. The results have demonstrated that aprotinin is a promising agent in the prevention of extraneural scarring.

The effect of low-dose external beam radiation on extraneural scarring after peripheral nerve surgery in rats.

OBJECTIVEScar tissue is an inevitable result of peripheral nerve surgery. A variety of substances have been used to prevent epineurial scarring. In this study, the effect of low-dose radiation therapy on epineurial scarring was investigated. METHODSSeventy-eight male Sprague-Dawley rats were studied. A total of 60 rats were subjected to one of three types of surgical procedure on the sciatic nerve, as follows: Procedure 1, external neurolysis (n = 20); Procedure 2, abrasive injury (n = 20); and Procedure 3, anastomosis (n = 20). On the left sciatic nerves, 700 cGy external beam radiation was administered 24 hours after surgery, and the right sciatic nerves served as a control group (surgery only). Eighteen animals without surgical intervention were used to establish the fibrotic effect of radiotherapy on normal nerves. A neurological examination was performed weekly. Six weeks after surgery, the extent of extraneural scarring was examined by gross microdissection by means of a numerical grading scheme and histological analysis. Cellular density and surface measurements of scar tissue were also evaluated. RESULTSThe dissection around the nerve was easier in rats treated with low-dose radiation compared with the control group. Furthermore, grading scores in both nerve adherence and nerve separability were significantly lower in treated nerves than in the control group (P ≤ 0.05). Low-dose radiotherapy decreased the scores of cellular density and surface measurement of scar tissue (P ≤ 0.05). In normal nerves, radiotherapy did not produce any fibrotic effects and the density of fibroblasts/fibrocytes was also very low. CONCLUSIONIn the case of surgery or local trauma to peripheral nerve, the use of low-dose radiation therapy may be a safe method of limiting postoperative epineurial scar formation.

Protective effect of the N-methyl-D-aspartate receptor antagonists, MK-801 and CPP on cold-induced brain oedema.

Summary Cold injury model in rat was used to determine the effect of treatment with the competitive NMDA antagonists CPP and the non-competitive NMDA antagonist MK-801 in cerebral oedema. MK-801 was applied in doses of 1 mg/kg and CPP of 10 mg/kg, 15 min. after injury. Control animals received 1 ml saline at the same time interval after injury. Tissue samples from the core and periphery of the lesion of the injured hemisphere and from the symmetrical location of the undamaged contralateral hemisphere were removed 24 hours after injury. Blood brain barrier permeability, brain water content and tissue specific gravity values were determined. MK-801 was found beneficial for reducing the oedema and restore the blood brain barrier permeability at the penumbral zone of the lesion, whereas both MK-801 and CPP were found ineffective for prevention of oedema accumulation at the core of the lesion.