Neuronal Damage In Patients Research Articles

Effects of Selenium and Topiramate on Cytosolic Ca2+ Influx and Oxidative Stress in Neuronal PC12 Cells

It has been widely suggested that selenium (Se) deficiency play an important role in the pathophysiology of epilepsy. It has been reported that Se provides protection against the neuronal damage in patients and animals with epilepsy by restoring the antioxidant defense mechanism. The neuroprotective effects of topiramate (TPM) have been reported in several studies but the putative mechanism of action remains elusive. We investigated effects of Se and TPM in neuronal PC12 cell by evaluating Ca(2+) mobilization, lipid peroxidation and antioxidant levels. PC12 cells were divided into eight groups namely control, TPM, Se, H(2)O(2), TPM + H(2)O(2), Se + H(2)O(2), Se + TPM and Se + TPM + H(2)O(2). The toxic doses and times of H(2)O(2), TPM and Se were determined by cell viability assay which is used to evaluate cell viability. Cells were incubated with 0.01 mM TPM for 5 h and 500 nM Se for 10 h. Then, the cells were exposed to 0.1 mM H(2)O(2) for 10 h before analysis. The cells in all groups except control, TPM and Se were exposed to H(2)O(2) for 15 min before analysis. Cytosolic Ca(2+) release and lipid peroxidation levels were higher in H(2)O(2) group than in control, Se and TPM combination groups although their levels were decreased by incubation of Se and TPM combination. However, there is no difference on Ca(2+) release in TPM group. Glutathione peroxidase activity, reduced glutathione and vitamin C levels in the cells were lower in H(2)O(2) group than in control, Se and TPM groups although their values were higher in the cells incubated with Se and TPM groups than in H(2)O(2) groups. In conclusion, these results indicate that Se induced protective effects on oxidative stress in PC12 cells by modulating cytosolic Ca(2+) influx and antioxidant levels. TPM modulated also lipid peroxidation and glutathione and vitamin C concentrations in the cell system.

Salivary neuron specific enolase: an indicator for neuronal damage in patients with ischemic stroke and stroke-prone patients

The blood-brain barrier is compromised in patients with stroke. The release of neuro-biochemical protein markers, such as neuron specific enolase (NSE) into the circulation may allow the pathophysiology and prognosis of patients with cerebrovascular diseases to be evaluated further. The present study was designed to measure the marker of neuronal damage, NSE, in saliva and serum of patients with acute ischemic stroke and patients with stroke related diseases as a diagnostic and/or monitoring tool for early prediction of ischemic stroke. Salivary and serum NSE concentrations were measured in 150 individuals. Fifty were patients recently diagnosed as having ischemic stroke, 75 were gender and age-matched risk-group patients (patients with hypertension, type 2 diabetes and ischemic heart disease). Another 25 were gender and age-matched healthy controls. Salivary and serum NSE concentrations were significantly higher than that of healthy controls. The cut-off threshold for salivary NSE of 3.7 microg/L was optimum, showing 80% accuracy for differentiation of ischemic stroke from normal individuals. Salivary NSE (alone or in combination with serum) can be used as a valuable diagnostic and possibly prognostic tool for measurement of neuronal damage in patients with stroke and stroke-related diseases.

Longitudinal analysis of regional grey matter loss in Huntington disease: effects of the length of the expanded CAG repeat

Background:The mechanisms guiding the progression of neuronal damage in patients with Huntington disease (HD) are not completely understood. It is unclear whether the genotype—that is, the length of the expanded...

The increase of neuron-specific enolase in cerebrospinal fluid and plasma as a marker of neuronal damage in patients with acute brain infarction

Our goal was to determine the neuron-specific enolase (NSE) concentration in cerebrospinal fluid (CSF) and plasma in patients with the acute brain infarction (BI) and analyze the correlation between the measured NSE concentration and infarct volume and the degree of neurological and functional deficit. The study included 55 patients aged 56-68 with BI in the acute phase. The control group consisted of 16 patients subjected to diagnostic radiculography. The results showed a significant increase of NSE concentration within the first seven days in patients compared to the controls (2.838 +/- 0.504 ng/ml CSF and 4.479 +/- 0.893 ng/ml plasma). A significant correlation was found between NSE concentration and infarction volume and the degree of neurological and functional deficit both in the CSF (r = 0.828, r = 0.735, r = 0.796; p < 0.001) and in plasma (r = 0.810, r = 0.681, r = 0.783; p < 0.001). The results suggest that an early determination of this marker in CSF and plasma in patients with BI could be a valuable diagnostic factor.

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Imaging

1663 Increase of cerebrospinal and plasma neuron specific enolase as a marker of neuronal damage in patients with acute brain infarction

1663 Increase of cerebrospinal and plasma neuron specific enolase as a marker of neuronal damage in patients with acute brain infarction

Quantitative head injury assessment: magnetic resonance spectroscopy and intensive care management during MR

Objective: To quantify central neuronal damage in patients with acute traumatic brain injury (TBI), to determine if brain tissue ischaemia was present using lactate as a marker, and to describe methods of delivering intensive anaesthetic care within a magnetic resonance scanner. Design: Patients underwent T2 weighted magnetic resonance and spectroscopic imaging (SI) early after TBI. Setting: A tertiary referral centre for neurosurgery and neurointensive care in Scotland. Subjects: Eight adults with TBI imaged 4-26 days (mean 13) after injury. Findings were compared to six healthy volunteer control subjects. Measurements and results: A significant reduction of N-acetyl aspartate (NAA- a neurone specific amino acid) was found in areas of brain with obvious lesions on T2 weighted imaging (p<0.001), and in areas where there were no obvious T2 lesions (p<0.02) compared with volunteer control spectra. We found no evidence of lactate. Conclusions: SI may be useful in assessing the extent of neuronal injury...

Quantitative head injury assessment: magnetic resonance spectroscopy and intensive care management during MR

Objective: To quantify central neuronal damage in patients with acute traumatic brain injury (TBI), to determine if brain tissue ischaemia was present using lactate as a marker, and to describe methods of delivering intensive anaesthetic care within a magnetic resonance scanner. Design: Patients underwent T2 weighted magnetic resonance and spectroscopic imaging (SI) early after TBI. Setting: A tertiary referral centre for neurosurgery and neurointensive care in Scotland. Subjects: Eight adults with TBI imaged 4-26 days (mean 13) after injury. Findings were compared to six healthy volunteer control subjects. Measurements and results: A significant reduction of N-acetyl aspartate (NAA- a neurone specific amino acid) was found in areas of brain with obvious lesions on T2 weighted imaging (p&lt;0.001), and in areas where there were no obvious T2 lesions (p&lt;0.02) compared with volunteer control spectra. We found no evidence of lactate. Conclusions: SI may be useful in assessing the extent of neuronal injury which compliments CT and MRI information. Traumatic brain injury affects all age groups and the associated morbidity has devastating consequences, SI may therefore assist clinicians in the management of these patients in the future. As demand for MR imaging of intensive care patients increases, clinicians will require to continue to develop safe working practices and maintain intensive care monitoring and therapies during these investigations.

Normalization of neuronal metabolic dysfunction after surgery for temporal lobe epilepsy. Evidence from proton MR spectroscopic imaging.

Surgery is a safe and effective treatment for patients with temporal lobe epilepsy (TLE) who do not respond adequately to anticonvulsant medication and in whom the seizure generator can be identified and safely removed. Proton MR spectroscopic imaging (MRSI) can image and quantify neuronal damage in patients with TLE based on reduced signals from N-acetylaspartate (NAA), a compound localized exclusively in neurons. We performed proton MRSI in patients with TLE before and after surgical treatment to determine whether NAA or other resonance intensities changed in the temporal lobes of patients with TLE after surgery, and whether these changes correlated with surgical outcome. N-acetylaspartate resonance intensity relative to creatine (NAA/Cr) was abnormally low preoperatively in at least one temporal lobe in all 14 patients examined. It was low ipsilaterally in the patients who became seizure free and bilaterally in those who did not. Postoperatively, it increased to the normal range on the side of surgery in all patients who became seizure free. In the one patient who became seizure free and who had low NAA/Cr in both temporal lobes before surgery, NAA/Cr values in the contralateral, unoperated temporal lobe also increased to the normal range. In contrast, NAA relative intensity ratios did not change in those patients who continued to have seizures after surgery. The creatine resonance intensity (Cr) in the temporal lobes was high, relative to the brainstem, in seven patients preoperatively. After surgery, the Cr remained high in two patients, both of whom continued to have seizures. We conclude that NAA (and Cr) abnormalities in TLE do not result solely from neuronal loss and gliosis but can be reversible after postsurgical control of seizures. This implies that the NAA and Cr abnormalities in patients with TLE, at least in part, are dynamic markers of both local and remote physiologic dysfunction associated with ongoing seizures.

A novel monoclonal antibody which reacts with a high molecular weight neuronal cytoplasmic protein and myelin basic protein (MBP) in a patient with macroglobulinemia

We report on the case of a 70-year-old man with primary macroglobulinemia who showed cranial polyneuropathy and extensive radiculoneuropathy. His serum contained an IgM λ monoclonal antibody which reacted with both a high molecular weight protein in grey matter and purified myelin basic protein (MBP) on immunoblotting. In an immunohistochemical study, strong immunoreactivity was detected only in the cytoplasm of neurons and weak immunoreactivity was detected in myelin. These findings suggest that this antibody may be related to the pathogenesis of neuronal damage in patients with macroglobulinemia.

Differential effects of chronic l-DOPA treatment on lipid peroxidation in the mouse brain with or without pretreatment with 6-hydroxydopamine

Whether or not chronic l-DOPA treatment (100 mg/kg, intraperitoneally (i.p.), twice daily for 4 weeks) alters lipid peroxidation in the brain as an indicator of neuronal damage was examined in normal mice and mice in which catecholamine (CA) neurons had been injured previously by the administration of 6-hydroxydopamine (6-OHDA), followed by recovery. In normal mice, chronic l-DOPA treatment reduced the thiobarbituric acid reacting substances (TBARS) level, an indicator of lipid peroxidation, in the cerebral cortex. In contrast, in mice with CA neuronal injury induced by pretreatment with 6-OHDA, the chronic l-DOPA treatment markedly increased the TBARS in the striatum and frontal cortex, despite recovery of the striatal dopamine levels similar to those in the control mice. These findings suggest that the long-term high-dose administration of l-DOPA enhances the progression of neuronal damage in patients with injured CA neurons such as those with Parkinson's disease.

Serum neurone specific enolase (NSE) levels as an indicator of neuronal damage in patients with cerebral infarction

A radioimmunoassay has been developed and used to measure serum neurone specific enolase (NSE) concentrations in 24 patients, following cerebral infarction. A significant correlation between cerebral infarct volume and maximum serum NSE concentration was observed (P = 0.047). Serum NSE was also assayed at times 24, 48, 72 and 96 h post ictus. At 72 h a significant correlation existed between serum NSE levels and infarct volume (P = 0.012), and levels appeared to be approaching statistical significance at 48 h (P = 0.067). No correlation existed at 24 and 96 h. In addition serum concentrations of NSE were compared to clinical outcome as determined by the Glasgow Outcome Score. Using the Mann-Whitney U test, there was no significant difference in maximum NSE level between patients graded 1-3 on the Glasgow Outcome Score and those graded 4 and 5. However, further studies are required on a larger population to more completely assess this. NSE may prove to be a useful marker of neuronal damage in the study of stroke, with particular application in the assessment of treatment.

Clinical Effects of Cerebral Revascularization combined with Isovolemic Hemodilution in Acute Stage of Ischemic Stroke

Superficial temporal artery-middle cerebral artery (STA-MCA) bypass is widely accepted as an effective treatment for ischemic cerebrovascular disease in terms of improvement of cerebral blood flow in the ischemic region. However, the indications for and timing of STA-MCA bypass in the acute stage of ischemic stroke have not been established. Isovolemic hemodilution has been shown to temporarily raise collateral perfusion in acutely ischemic brain regions distal to occluded cerebral arteries. The authors performed isovolemic hemodilution in 26 cases of cerebral ischemia within 72 hours of the onset of symptoms. This resulted in a 30% increase in regional cerebral blood flow (rCBF) in the area supplied by the affected MCA, leading to rapid neurological improvement in 18 patients. Nine of these 18 were randomly assigned to the early bypass group, in which STAMCA bypass was performed within 2 days of hemodilution. In the delayed bypass group, which included the remaining nine patients, bypass was performed more than 30 days after hemodilution. In the early group, rCBF in the affected MCA region increased by 18% and the neurological score (NS) improved by 10% within 1 month postoperatively. In the delayed group, follow-up examination 1 to 2 months after hemodilution, rCBF in the affected MCA region and NS had returned nearly to pretreatment levels. Moreover, in this group STA-MCA bypass improved neither rCBF nor neurological status. It can be concluded that isovolemic hemodilution temporarily increases rCBF in the ischemic territory and enhances the potential reversibility of neuronal damage in patients with acute ischemic stroke. Neuronal damage may be reversed and rCBF may be significantly improved if blood flow is re-established by surgical means (STA-MCA bypass) within hours or days following hemodilution.