Sevin Balkan

Utility of transcranial doppler ultrasonography for confirmatory diagnosis of brain death: two sides of the coin.

Background. Although the clinical examination and documentation of the clinical signs of brain death are very uniform, there are significant differences in the guidelines for using technical confirmatory tests to corroborate the clinical signs. The current study examined the utility of transcranial Doppler ultrasonography (TCD) for confirmation of brain death. Methods. After 19 patients were excluded from the study because of lack of bone window or because an apnea test could not be performed because of desaturation, 100 patients (61 patients with clinical brain death, and 39 control patients with Glasgow Coma Score<5) were included in the study. The following TCD findings were accepted as confirmatory of brain death when they were found bilaterally or in at least three different arteries for at least 3 minutes within the same examination: (1) brief systolic forward flow or systolic spikes and diastolic reverse flow, (2) brief systolic forward flow or systolic spikes and no diastolic flow, or (3) no demonstrable flow in a patient in whom flow had been clearly documented in a previous TCD examination. Results. The sensitivity and specificity of the first TCD examination for confirmation of brain death were 70.5% and 97.4%, respectively. Eighteen patients with clinical brain death required repeat TCD examinations because of detection of forward systolo-diastolic flow or a diastolic to-and-fro flow pattern, which were not confirmatory for the diagnosis of brain death. Brain death was confirmed ultrasonographically in 12 of 18 patients in a second examination after 12.6±8.3 hours of clinical brain death, in 2 patients in a third TCD examination, and in 1 patient in a fourth examination. Three clinically brain-dead patients had died before the diagnosis was confirmed by repeat TCD examinations. The sensitivity of TCD reached 100% in our study population after the fourth examination. Conclusion. The sensitivity of TCD is increased with repeat examinations and should be repeated in cases in which systolo-diastolic forward flow is demonstrated after the first TCD. TCD may prolong or shorten the time to declaration of brain death. The necessity of demonstrating cerebral circulatory arrest in patients with clinical brain death is debatable.

Lipid peroxidation in rat brain during focal cerebral ischemia: prevention of malondialdehyde and lipid conjugated diene production by a novel antiepileptic, lamotrigine.

The effects of Lamotrigine (LTG) which blocks ischemia induced glutamate (Glu) release, on lipid peroxidation have been evaluated in cortical and cerebellar tissues of rat brain during focal cerebral ischemia. A total of 45 rats were randomly assigned into one of four groups; sham operated animals as controls, animals subjected to middle cerebral artery occlusion (MCAO) and treatment groups with LTG (20 mg/kg i.p.) either 30 min before or just after MCAO. Changes in lipid peroxides were expressed as nanomoles of malondialdehyde (MDA) and conjugated diene (CD) per milligram of protein. MDA values following 60 min of ischemia relative to contralateral cortex and CD levels in 0, 10 and 60 min of ischemia were found to be higher in the ipsilateral cortex than those in the contralateral cortex. On the other hand, contralateral cerebellar MDA levels after 0 and 60 min of ischemia and CD levels after 0, 10 and 60 min of ischemia were higher than those in the ipsilateral cerebellum. Pharmacological inhibition of Glu release significantly decreased the MDA and CD production in both cortex and cerebellum. Pre- or post-ischemic administration of LTG did not significantly change CD levels, but MDA levels in contralateral cortex were found to be significantly decreased than those in ischemic cortex in both pre- and post-treated group.

Orthostatic heart rate variability analysis in idiopathic Parkinson's disease

Objectives –  We evaluated time and spectral analyses of 24‐h heart rate variability (HRV) and the heart rate responses to passive tilt in patients with idiopathic Parkinsons disease (IPD) in order to investigate cardiovascular autonomic functions.

Inhibitory role of Nω-nitro-l-arginine methyl ester (L-NAME), a potent nitric oxide synthase inhibitor, on brain malondialdehyde and conjugated diene levels during focal cerebral ischemia in rats

The effect of N omega-nitro-L-arginine methyl ester (L-NAME) on ischemic neuronal damage was studied in a rat model of permanent focal cerebral ischemia in terms of ipsilateral and contralateral cortical and cerebellar tissue lipid peroxides. Forty-five male Swiss Albino rats were assigned to one of four groups; sham operated as control, subjected to right middle cerebral artery occlusion or injection of L-NAME (10 mg/kg i.p.) either 30 min before or just after right middle cerebral artery occlusion. Changes in lipid peroxides were expressed as nanomoles of malondialdehyde and conjugated diene per milligram of protein. Malondialdehyde values following 60 min of ischemia relative to contralateral cortex and conjugated diene levels in 0, 10 and 60 min of ischemia were found to be higher in ipsilateral cortex than in contralateral cortex. On the other hand, contralateral cerebellar malondialdehyde levels after 0 and 60 min of ischemia and conjugated diene levels after 0, 10 and 60 min of ischemia were higher than those in ipsilateral cerebellum. Pharmacological inhibition of nitric oxide synthase by L-NAME before or just after permanent middle cerebral artery occlusion significantly decreased the malondialdehyde and conjugated diene levels in both the cortex and the cerebellum. No significant differences were found in malondialdehyde values between rats that had been pre- and post-treated with L-NAME, but conjugated diene levels in the post-treated group seemed to be significantly lower than those in the pretreated group. On the whole, these results suggest that malondialdehyde and conjugated diene represent early biochemical markers of lipid peroxidation in ischemic tissues, reflecting the radical-mediated tissue damage.

Effects of Lamotrigine on brain nitrite and cGMP levels during focal cerebral ischemia in rats

Glutamate receptor antagonists are protective in animal models of focal cerebral ischemia. Lamotrigine (3,5‐diamino‐6‐[2,3‐dichlorophenyl]‐1,2,4‐triazine) is an anticonvulsant drug that blocks voltage‐gated sodium channels and inhibits the ischemia‐induced release of glutamate. Experiments in primary neuronal cultures implicate nitric oxide (NO) as a mediator of glutamatergic neurotoxicity acting via N‐Methyl‐d‐Aspartate (NMDA) receptors. The effect of glutamate release inhibitor, Lamotrigine upon NO and cGMP production has been examined in focal cerebral ischemia in rats. Focal cerebral ischemia was produced by the permanent occlusion of right middle cerebral artery (MCA) in urethane anesthetized rats. A number of indicators of brain NO production (nitrite, cGMP) were determined in ipsilateral and contralateral cerebral cortex and cerebellum after 0, 10, 60 min of focal cerebral ischemia. The same parameters were measured in rats treated with Lamotrigine (20 mg/kg, i.p.) 30 min before or just after the occlusion of the right MCA.

The effects of NMDA receptor antagonist MK-801 on lipid peroxidation during focal cerebral ischemia in rats.

The effect of MK-801 on ischemic neuronal damage was studied in a rat model of permanent focal cerebral ischemia in terms of ipsilateral and contralateral cortical and cerebellar tissue lipid peroxides. Forty-five male Swiss Albino rats were assigned into one of four groups: sham operated as controls, subjected to right middle cerebral artery occlusion (MCAO) or injection of MK-801 (0.5 mg/kg i.p.) either 30 min before or just after right MCAO. Changes in lipid peroxides were expressed as nmol malondialdehyde (MDA) and conjugated diene (CD)/mg protein. MDA values after 60 min of ischemia relative to contralateral cortex and CD levels in 0, 10 and 60 min after ischemia were found to be higher in ipsilateral cortex than those in contralateral cortex. On the other hand, contralateral cerebellar MDA levels in 0 and 60 min of ischemia and CD levels in 0, 10 and 60 min after ischemia were found to be higher than those in ipsilateral cerebellum. Pharmacological inhibition of glutamate receptor by MK-801 before or just after permanent MCAO decreased significantly the MDA and CD levels in both cortex and cerebellum. Although no significant differences found in MDA values between rats pre- and posttreated with MK-801, CD levels in posttreated group seemed significantly lower than those in pretreated group. On the whole, these results suggest that MDA and CD represent early biochemical marker of lipid peroxidation in ischemic tissues, reflecting the radical-mediated tissue damage.

The effects of citicoline and lamotrigine alone and in combination following permanent middle cerebral artery occlusion in rats.

The neuroprotective efficacies of citicoline and lamotrigine, alone and in combination, were investigated in experimental permanent focal ischemia. Seven groups of adult male rats underwent focal cerebral ischemia and were given the following treatments: placebo (P), low and high doses of citicoline (C250 and C500, 250 and 500 mg/kg/day i.p., respectively), low and high doses of lamotrigine (L50 and L100, 50 and 100 mg/kg/day p.o., respectively), and combination regimes of both drugs in low (C250 + L50) and high doses (C500 + L100). Citicoline, but not lamotrigine, exerted neuroprotective efficacy during this acute ischemic stroke model. The citicoline and lamotrigine combination did not provide a significant additive neuroprotective effect

Biochemical evidence of crossed cerebellar diaschisis in terms of nitric oxide indicators and lipid peroxidation products in rats during focal cerebral ischemia

Objectives – Cerebral hypoperfusion in the contralateral cerebellar hemisphere after stroke is interpreted as a functional and metabolic depression, possibly caused by a loss of excitatory afferent inputs on the corticopontocerebellar pathway terminating in the cerebellar gray matter. This phenomenon is defined as crossed cerebellar diaschisis and can be diagnosed clinically by positron emission tomography, single‐photon emission computed tomography, brain magnetic resonance imaging and electroencephalography in terms of regional cerebral blood flow or metabolic rate of oxygen measurements. Materials and methods – In the present study, nitric oxide indicators (nitrite and cyclic guanosine monophosphate) and lipid peroxidation products (malondialdehyde and conjugated dienes) were measured in rat cerebral cortices and cerebella after permanent right middle cerebral artery occlusion in order to assess the crossed cerebellar diaschisis. Results – Nitrite values in ipsilateral cortex were significantly higher than those in contralateral cortex at 10 (P<0.001) and 60 (P<0.05) min of ischemia but no significant changes were observed in both cerebellum compared to the 0 min values. In both cerebral cortex and cerebellum cGMP levels at 10 and 60 min were significantly increased (P<0.001). This increase was marked in ipsilateral cortex and contralateral cerebellum when compared with opposite cortex and cerebellum (P<0.001). MDA values in ipsilateral cortex were significantly higher than those in contralateral cortex at 60 min of ischemia (P<0.05). Contralateral cerebellar MDA values were found significantly higher than those in ipsilateral cerebellum at 0 (P<0.001) and 60 (P<0.05) min of ischemia. In ipsilateral cortex, conjugated diene values at 0, 10, 60 min of ischemia were higher than those in contralateral cortex. On the other hand 0, 10, 60 min conjugated diene levels in contralateral cerebellum were significantly higher than those in ipsilateral cerebellum (P<0.001). Conclusion – These findings support the interruption of the corticopontocerebellar tract as the mechanism of the crossed cerebellar diaschisis.

The effects of nitric oxide synthase inhibitor, L-NAME on NO production during focal cerebral ischemia in rats: could L-NAME be the future treatment of sudden deafness?

Recent evidence in primary neuronal cell culture implicates NO as a mediator of glutamatergic neurotoxicity acting via N-methyl-D-aspartate (NMDA) receptors. In this study, we investigated the effects of inhibition of NOsynthase activity in focal cerebral ischemia in rats. Focal cerebral ischemia was produced by permanent occlusion of right MCA in urethane anesthetized rats. A number of indicators of brain NO production, nitrite and cGMP were determined in ipsilateral and contralateral cerebral cortex and cerebellum after 0, 10 and 60 minutes of focal cerebral ischemia. The same parameters were measured in rats pre- and posttreated with the potent Nitric oxide synthase (NOS) inhibitor, NW-nitro-L-arginine methyl ester (L-NAME).

Normalization of high interictal cerebrovascular reactivity in migraine without aura by treatment with flunarizine.

Background.—Modification of migraine‐associated cerebrovascular reactivity may provide insight into the mechanism of action of a given therapeutic intervention.