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Biomedical subjects

M K Başkaya

Publications and source records attributed to M K Başkaya.

At least 19 recordsLinked to original sources
PubMed2001

Type III occipital condylar fracture presenting with hydrocephalus, vertebral artery injury and vasospasm: case report.

Occipital condylar fractures (OCF) are rare and have a high mortality rate. We report a patient with OCF who presented with acute hydrocephalus and died from diffuse vasospasm secondary to vertebral artery injury. A 45-year-old man fell 20 feet from a deer stand and landed on his head. CT showed a type III OCF continuing to the anterior rim of the foramen magnum on the left, with a bone fragment pushing into the medulla, causing hydrocephalus. The patient was stabilized, and a four-vessel arteriogram showed diffuse vasospasm with complete occlusion of the left vertebral artery at the level of the OCF. To our knowledge, this is the first documented case of the conjunction of OCF, hydrocephalus, and vasospasm.

Accidental Falls↗
PubMed2001

Results of surgical treatment of intrasylvian hematomas due to ruptured intracranial aneurysms.

In this retrospective study, the surgical outcome of patients with intrasylvian hematomas due to rupture of intracranial aneurysms was analyzed. The authors studied ten patients who underwent aneurysm surgery and evacuation of the hematoma within 12 h of the onset of bleeding. All patients had an intrasylvian hematoma classified with computerized tomography and all patients underwent pre-operative angiography. In all patients, the origin of bleeding was a middle cerebral artery aneurysm, with the exception of one patient whose bleeding originated from a posterior communicating artery aneurysm. Three patients achieved good recovery without any significant neurological deficit and four achieved good recovery with moderate disabilities. One patient died due to pneumonia and two were in a vegetative state. Notably, three patients who were comatose (Hunt and Hess Grade V) at the time of presentation achieved good recovery following surgery. In this study, neurological status at presentation did not predict the outcome. The only significant prognostic factor in those patients who had intrasylvian hematoma was early surgery within 12 h of the bleeding. We suggest that early surgical treatment be performed in patients with intrasylvian hematoma, regardless of the neurological findings and grade on admission. Pre-operative angiography seems to be essential in identifying the source of bleeding.

Adult↗
PubMed2000

Application of 2,3,5-triphenyltetrazolium chloride staining to evaluate injury volume after controlled cortical impact brain injury: role of brain edema in evolution of injury volume.

A reliable method for measuring injury volume after traumatic brain injury (TBI) is of great importance when studying pharmacological protective agents in the field of head trauma research. Utilization of 2,3,5-triphenyltetrazolium chloride (TTC) has gained extensive acceptance in stroke research and has recently been applied to injury volume measurement in the lateral fluid percussion model. The present study was undertaken to apply this method to the controlled cortical impact (CCI) model and to study the role of brain edema. Male Sprague-Dawley rats were subjected to CCI brain injury at a velocity of 3 m/sec and 1 mm (mild), 2 mm (moderate), and 3 mm (severe injury) deformation, while rats in the control group were subjected to the same surgical procedure but received no injury. Absolute and corrected injury volumes with TTC staining and brain edema measurements with the wet-dry method were evaluated at 1, 2, 3, 4, and 7 days after TBI. The most prominent injury volume in the moderate injury group (2 mm deformation) was seen at postinjury day 1 and 2 (day 1, absolute: 49.1+/-5.6, corrected: 40.5+/-7.9; day 2, absolute: 46+/-6.9, corrected: 40.2+/-10.5), whereas the smallest injury volume was found at postinjury day 7 (absolute: 24.9+/-7, corrected: 27.4+/-7.4). The time course of brain edema studies demonstrates that brain edema formation peaks at postinjury day 1. A statistically significant reduction of injury volume was observed after postinjury day 4. We also observed that due to the presence of brain edema absolute injury volume is more than corrected injury volume in the first 3 days after injury as opposed to injury volume at postinjury day 7. These results suggest that the measurement of injury volume with TTC staining should be corrected for brain edema in the CCI brain injury model.

Animals↗
PubMed2000

Attenuation of brain edema, blood-brain barrier breakdown, and injury volume by ifenprodil, a polyamine-site N-methyl-D-aspartate receptor antagonist, after experimental traumatic brain injury in rats.

OBJECTIVE: Traumatic brain injury (TBI) has been shown to induce a significant change in polyamine metabolism. Polyamines and polyamine-dependent calcium influx play an important role in mediating the effects of excitotoxic amino acids at the N-methyl-D-aspartate (NMDA) receptor site. We studied the effects of ifenprodil, known as a noncompetitive inhibitor of polyamine sites at the NMDA receptor, on brain edema formation, blood-brain barrier breakdown, and volume of injury after TBI. METHODS: Experimental TBI was induced in Sprague-Dawley rats by a controlled cortical impact device, functioning at a velocity of 3 m/s to produce a 2-mm deformation. Ifenprodil or saline (10 mg/kg) was injected intraperitoneally immediately after the cortical impact injury and then every 90 minutes until 6 hours after TBI. Blood-brain barrier breakdown was evaluated quantitatively 6 hours after injury by fluorometric assay of Evans blue extravasation. Brain water content, an indicator of brain edema, was measured with the wet-dry method 24 hours after TBI. Injury volume was quantitated from the brain slices stained with 2% cresyl violet solution 7 days after TBI. RESULTS: Blood-brain barrier breakdown was significantly lower in the traumatic cortex of the ifenprodil-treated group than in the saline-treated group (84.4 +/- 26.8 microg/g versus 161.8 +/- 27 microg/g, respectively, P < 0.05). Brain edema was significantly reduced in the cortex of the ifenprodil-treated group relative to that in the saline-treated group (80.9 +/- 0.5% versus 82.4 +/- 0.6% respectively, P < 0.05). Ifenprodil treatment reduced injury volume significantly (14.9 +/- 8.1 mm3 versus 24.4 +/- 6.7 mm3, P < 0.05). CONCLUSION: The polyamine-site NMDA receptor antagonist ifenprodil affords significant neuroprotection in a controlled cortical impact brain injury model and may hold promise for the discovery and treatment of the mechanism of delayed neurological deficits after TBI.

Animals↗
PubMed2000

Neuroprotective effects of citicoline on brain edema and blood-brain barrier breakdown after traumatic brain injury.

OBJECT: Cytidine 5'-diphosphocholine (CDPC), or citicoline, is a naturally occurring endogenous compound that has been reported to provide neuroprotective effects after experimental cerebral ischemia. However, in no study has such protection been shown after traumatic brain injury (TBI). In this study the authors examined the effect of CDPC on secondary injury factors, brain edema and blood-brain barrier (BBB) breakdown, after TBI. METHODS: After anesthesia had been induced in Sprague-Dawley rats by using 1.5% halothane, an experimental TBI was created using a controlled cortical impact (CCI) device with a velocity of 3 m/second, resulting in a 2-mm deformation. Four sham-operated control animals used for brain edema and BBB breakdown studies underwent the same surgical procedure, but received no injury. Brain edema was evaluated using the wet-dry method 24 hours postinjury, and BBB breakdown was evaluated by measuring Evans blue dye (EBD) extravasation with fluorescein 6 hours after TBI. The animals received intraperitoneal injections of CDPC (50, 100, or 400 mg/kg two times after TBI [eight-10 animals in each group]) or saline (eight animals) after TBI. Traumatic brain injury induced an increase in the percentage of water content and in EBD extravasation in the injured cortex and the ipsilateral hippocampus. No significant benefit from CDPC treatment was observed at a dose of 50 mg/kg. Cytidine 5'-diphosphocholine at a dose of 100 mg/kg attenuated EBD extravasation in both regions, although it reduced brain edema only in the injured cortex. In both regions, 400 mg/ kg of CDPC significantly decreased brain edema and BBB breakdown. CONCLUSIONS: This is the first report in which dose-dependent neuroprotective effects of CDPC have been demonstrated in the injured cortex as well as in the hippocampus, a brain region known to be vulnerable to injury, after experimental TBI. The results of this study suggest that CDPC is an effective neuroprotective agent on secondary injuries that appear following TBI.

Animals↗
PubMed1999

Effects of MDL 72527, a specific inhibitor of polyamine oxidase, on brain edema, ischemic injury volume, and tissue polyamine levels in rats after temporary middle cerebral artery occlusion.

The possible effects of the polyamine interconversion pathway on tissue polyamine levels, brain edema formation, and ischemic injury volume were studied by using a selective irreversible inhibitor, MDL 72527, of the interconversion pathway enzyme, polyamine oxidase. In an intraluminal suture occlusion model of middle cerebral artery in spontaneously hypertensive rats, 100 mg/kg MDL 72527 changed the brain edema formation from 85.7 +/- 0.3 to 84.5 +/- 0.9% in cortex (p < 0.05) and from 79.9 +/- 1.7 to 78.4 +/- 2.0% in subcortex (difference not significant). Ischemic injury volume was reduced by 22% in the cortex (p < 0.05) and 17% in the subcortex (p < 0.05) after inhibition of polyamine oxidase by MDL 72527. There was an increase in tissue putrescine levels together with a decrease in spermine and spermidine levels at the ischemic site compared with the nonischemic site after ischemia-reperfusion injury. The increase in putrescine levels at the ischemic cortical and subcortical region was reduced by a mean of 45% with MDL 72527 treatment. These results suggest that the polyamine interconversion pathway has an important role in the postischemic increase in putrescine levels and that blocking of this pathway can be neuroprotective against neuronal cell damage after temporary focal cerebral ischemia.

Animals↗
PubMed1999

Application of endovascular suture occlusion of middle cerebral artery in gerbils to obtain consistent infarction.

Middle cerebral artery occlusion (MCAO) by endovascular suture has gained increasing acceptance because it is relatively non-invasive and allows reperfusion. However, its application in rats has resulted in inconsistent infarction volumes which involve only the subcortex or subcortex plus some cortex. In order to eliminate this drawback, we applied the intraluminal suture occlusion of MCA to gerbils that have an incomplete Circle of Willis. MCAO was induced by inserting an endovascular 5-0 nylon suture with a blunted tip into the Circle of Willis. Animals were divided into two groups: permanent MCAO for 24 h (n = 8) and transient MCAO for 3 h with 21 h reperfusion (n = 8). The corrected infarction volume in the permanent MCAO group was 232 +/- 37 mm3 whereas it was 230 +/- 45 mm3 in the transient MCAO group. All animals in both groups had infarction in both cortex and subcortex. Results of this study show that endovascular suture occlusion of MCA can be easily applied in gerbils to obtain consistent infarction. This would allow both transient and permanent focal ischemia to be tested in the same model of ischemia.

Animals↗
PubMed1998

Increased ornithine decarboxylase activity and protein level in the cortex following traumatic brain injury in rats.

There is increasing evidence that the elevated levels of polyamines play an important role in the secondary injury following traumatic brain injury (TBI). Ornithine decarboxylase (ODC) is the rate-limiting enzyme of polyamine biosynthesis. Presently, we measured the ODC protein levels by Western blot analysis in the cerebral cortex of rats sacrificed at 2 h, 6 h, 24 h, 72 h and 168 h after controlled cortical impact injury. TBI resulted in a significant increase in ODC protein levels (2.5 to 5.5 fold, P<0.05) and enzyme activity (13 to 21 fold, p<0.01) between 2 and 6 h after the injury. ODC protein levels and enzyme activity returned to normal, control levels by 72 h after the injury. Increased ODC protein and enzyme activity could contribute to vasogenic edema and the pathogenesis of neuronal dysfunction after TBI by stimulating the formation of polyamines.

Animals↗
PubMed1998

Traumatic brain injury down-regulates glial glutamate transporter (GLT-1 and GLAST) proteins in rat brain.

Excess activation of NMDA receptors is felt to participate in secondary neuronal damage after traumatic brain injury (TBI). Increased extracellular glutamate is active in this process and may result from either increased release or decreased reuptake. The two high-affinity sodium-dependent glial transporters [glutamate transporter 1 (GLT-1) and glutamate aspartate transporter (GLAST)] mediate the bulk of glutamate transport. We studied the protein levels of GLT-1 and GLAST in the brains of rats after controlled cortical impact-induced TBI. With use of subtype-specific antibodies, GLT-1 and GLAST proteins were quantitated by immunoblotting in the ipsilateral and contralateral cortex at 2, 6, 24, 72, and 168 h after the injury. Sham-operated rats served as control. TBI resulted in a significant decrease in GLT-1 (by 20-45%; p < 0.05) and GLAST (by 30-50%; p < 0.05) protein levels between 6 and 72 h after the injury. D-[3H]Aspartate binding also decreased significantly (by 30-50%; p < 0.05) between 6 and 72 h after the injury. Decreased glial glutamate transporter function may contribute to the increased extracellular glutamate that may mediate the excitotoxic neuronal damage after TBI. This is a first report showing altered levels of glutamate transporter proteins after TBI.

ATP-Binding Cassette Transporters↗
PubMed1998

Intraluminal suture occlusion of the middle cerebral artery in Spontaneously Hypertensive rats.

In models of middle cerebral artery occlusion using intraluminal suture, the size and the distribution of ischemic injury vary considerably among laboratories. In transcranial models of cerebral ischemia, a more consistent cerebral ischemic lesion is seen in Spontaneously Hypertensive rats (SHR). In the present study, we performed intraluminal suture occlusion of the MCA in SHR and compared its reproducibility with those in Sprague-Dawley (SD) rats. Male SHR and SD rats were anesthetized with halothane and subjected to 2 h of temporary middle cerebral artery occlusion by an intraluminal suture. Comparisons of regional cerebral blood flow figures taken throughout the experiment and lesion volume figures taken at 24 h after occlusion were made between the two groups. Total lesion volume in the SHR group was 263.6+/-30.5 mm3 (mean +/- SD), significantly larger and less variable than that in the SD group (145.4+/-123.7 mm3, p < 0.02). Throughout the ischemic period there was a tendency for rCBF to be lower in the SHR group than in the SD group. In some animals of both groups, recirculation could not be produced by withdrawal of the suture from the ICA. The mortality rate was 9% in the SD group and 17% in the SHR group. Intraluminal MCA occlusion in SHRs is associated with a more consistent, reliable and reproducible volume of ischemic injury. In the studies of temporary focal cerebral ischemia, this model must be accompanied by the monitoring of regional cerebral blood flow so as to obtain more reliable results.

Age Factors↗
PubMed1997

The biphasic opening of the blood-brain barrier in the cortex and hippocampus after traumatic brain injury in rats.

This study examined the time course of the blood-brain barrier (BBB) opening and correlated this with brain edema formation after a lateral controlled cortical impact (CCI) brain injury in rats. Quantitative measurement of Evans blue (EB) extravasation using fluorescence was employed at 2, 4, 6 h and 1, 2, 3, 4 and 7 days after injury. Brain edema was measured by specific gravity of the tissue at corresponding time points. Two prominent EB extravasations were observed at 4-6 h and 3-day after injury in the injury-site cortex and the ipsilateral hippocampus. Brain edema became progressively more severe over time and peaked at 24 h after injury and began to decline after day 3. These results suggest that there is a biphasic opening of the BBB after CCI brain injury and the second opening of the BBB does not contribute to a further increase in edema formation.

Animals↗
PubMed1997

Regional brain polyamine levels in permanent focal cerebral ischemia.

Transient global cerebral ischemia has been shown to induce marked changes in the polyamine pathway with a significant increase in putrescine, the product of the ornithine decarboxylase reaction. This study examined the relationship between tissue and extracellular polyamines and regional cerebral blood flow and brain edema. Six hours of focal ischemia in cats (n = 10) was produced by permanent middle cerebral artery occlusion. Extracellular polyamines were measured in extracellular fluid obtained by microdialysis. Regional cerebral blood flow using laser Doppler flowmetry and specific gravity, an indicator of brain edema, were measured in contralateral (non-ischemic), penumbra and densely ischemic brain regions. A significant increase in the tissue putrescine level was found in the penumbra but there was no difference in the putrescine levels between contralateral and densely ischemic regions. There was no significant change in the spermidine and spermine levels in the three regions. Extracellular levels of putrescine and spermidine were found to be significantly lower than the tissue levels and no change in polyamines was observed in any region. Significant edema formation was observed in densely ischemic and penumbra regions. This is the first demonstration that tissue putrescine is increased in the penumbra region, an area of incomplete ischemia that is developing brain edema.

Animals↗
PubMed1997

Beneficial effects of S-adenosyl-L-methionine on blood-brain barrier breakdown and neuronal survival after transient cerebral ischemia in gerbils.

We have studied the beneficial effects of S-adenosyl-L-methionine (SAM) tosylate on blood-brain barrier (BBB) breakdown and neuronal survival after transient cerebral ischemia in gerbils. BBB breakdown experiments were performed in pentobarbital anesthetized gerbils subjected to 10 min of bilateral carotid artery occlusion and 6 h of reperfusion. For BBB breakdown measurements, SAM (120 mg/kg, i.p.) was administered to gerbils just after occlusion and thereafter every hour up to 5 h. Fluorometric measurements quantified the blood-brain permeability tracer, Evans blue (EB). SAM treatment significantly reduced the BBB breakdown as indicated by reduced levels of EB fluorescence. Neuronal count experiments were conducted in gerbils subjected to transient ischemia and 7 days of reperfusion. For neuronal count experiments SAM (15-120 mg/kg) was administered at 6 and 12 h after reperfusion, and twice each day thereafter for 7 days. SAM dose dependently protected the hippocampal CA1 neurons assessed by histopathological methods. SAM has a beneficial effect on the outcome of ischemic injury by reducing the BBB breakdown and neuronal death.

Animals↗
PubMed1997

Protective effects of ifenprodil on ischemic injury size, blood-brain barrier breakdown, and edema formation in focal cerebral ischemia.

OBJECTIVE: Ifenprodil, a polyamine site N-methyl-D-aspartate receptor/channel antagonist, has been reported to decrease infarction volume after cerebral ischemia. However, the possible mechanisms of this protective effect have not been studied in detail. We investigated the effects of ifenprodil on ischemic injury size, blood-brain barrier (BBB) permeability, regional brain edema, and cerebral blood flow. METHODS: Focal ischemia for 6 hours was produced by permanent occlusion of the middle cerebral artery in 15 anesthetized cats. Treatment with drug (n = 8) or vehicle (n = 7) was initiated at 5 minutes after ischemia and continued for 3 hours. Physiological variables were continuously monitored during experiments. We measured ischemic injury size, brain edema, and BBB permeability to Evans blue and determined regional cerebral blood flow by using laser doppler flowmetry. RESULTS: Both ischemic injury size and BBB permeability were smaller in the ifenprodil-treated group, compared with the saline-treated group (P < 0.05). Ifenprodil treatment also attenuated brain edema formation in the dense ischemic region, compared with saline treatment (1.035 +/- 0.002 versus 1.028 +/- 0.002, P < 0.05). There was no significant change in cerebral blood flow with ifenprodil treatment. CONCLUSION: Findings from this study confirm that ifenprodil treatment results in a significant decrease in the size of ischemic injury after focal ischemia. The tissue-sparing effect of ifenprodil is not related to its vasoactive properties. It is likely that its neuroprotective effects are related to its ability to antagonize N-methyl-D-aspartate receptors, which results in a decrease in brain edema and BBB permeability.

Animals↗
PubMed1997

Effects of ifenprodil, a polyamine site NMDA receptor antagonist, on reperfusion injury after transient focal cerebral ischemia.

Polyamines and N-methyl-D-aspartate (NMDA) receptors are both thought to play an important role in secondary neuronal injury after cerebral ischemia. Ifenprodil, known as a noncompetitive inhibitor of polyamine sites at the NMDA receptor, was studied after transient focal cerebral ischemia occurred. Spontaneously hypertensive male rats, each weighing between 250 and 350 g, underwent 3 hours of tandem middle cerebral artery (MCA) and common carotid artery occlusion followed by reperfusion for a period of 3 hours or 21 hours. Intravenous ifenprodil (10 microg/kg/minute) or saline infusion was started immediately after the onset of MCA occlusion and continued throughout the ischemic period. Physiological parameters including blood pressure, blood gas levels, blood glucose, hemoglobin, and rectal and temporal muscle temperatures were monitored. Six rats from each group were evaluated at 6 hours postocclusion for brain water content, an indicator of brain edema, and Evans blue dye extravasation for blood-brain barrier breakdown. Infarct volume was also measured in six rats from each group at 6 and 24 hours postocclusion. Ifenprodil treatment significantly reduced brain edema (82.5 +/- 0.4% vs. 83.5 +/- 0.4%, p < 0.05) and infarct volume (132 +/- 14 mm3 vs. 168 +/- 25 mm3, p < 0.05) compared with saline treatment, with no alterations in temporal muscle (brain) or rectal (body) temperature (35.9 +/- 0.4 degrees C vs. 36.2 +/- 0.2 degrees C; 37.7 +/- 0.4 degrees C vs. 37.6 +/- 0.6 degrees C; not significant). These results demonstrate that ifenprodil has neuroprotective properties after ischemia/reperfusion injury in the absence of hypothermia. This indicates that antagonists selective for the polyamine site of the NMDA receptors may be a viable treatment option and helps to explain some of the pathophysiological mechanisms involved in secondary injury after transient focal cerebral ischemia has occurred.

Adrenergic alpha-Antagonists↗