The effects of environmental light--dark changes on experimental mild traumatic brain injury.

OBJECTIVES: The aim of this study was to investigate the effects of environmental light-dark changes on the outcome of mild traumatic brain injury (MTBI) using an experimental rodent model. The functions of endogenous and exogenous melatonin on the outcome of injury were also investigated METHODS: Mild traumatic brain injury was experimentally induced in 56 male Sprague-Dawley rats using a weight-drop device. Animals were divided into four groups of 14 each as follows: (i) sham-operated (trauma only, normal day-night cycle), (ii) treated with melatonin (trauma+melatonin, normal day-night cycle), (iii) darkness-induced (trauma+48 h constant dark), and (iv) treated with melatonin and darkness-induced (trauma+48 h constant dark+melatonin). Melatonin (50 mg/kg) was administered, intraperitoneally, immediately after trauma. EEG recordings were taken at three time periods (pretrauma, immediately after trauma, and 48 h after trauma). Motor functions were tested pretrauma, 24 and 48 h post-trauma. Serum melatonin levels were determined pretrauma and 48 h post-trauma. Tissue samples from right frontal area were taken 48 h after trauma for light and electron microscopic examinations. CONCLUSION: Following MTBI light deprivation alone and light deprivation in combination with exogenously administered melatonin indicated significant neuroprotective effects. Although there may be other important pathways, darkness-induced elevation in endogenous melatonin secretion appears to play an important role in this neuroprotective outcome.

Brainstem auditory and visual evoked potentials in children with protein-energy malnutrition.

BACKGROUND: To determine the effects of malnutrition on the developing brain with brainstem auditory evoked potentials (BAEP) and flash visual evoked potentials (fVEP). METHODS: The BAEP and fVEP of 11 kwashiorkor (8 +/- 1.56 months) and 10 marasmus (7.9 +/- 1.27 months) patients and 10 healthy control subjects (7.65 +/- 0.82 months) were recorded and the measurements were compared with each other in relation with plasma total protein and albumin levels. RESULTS: There were no differences between the mean latencies of the waves I, II, III and IV and mean interpeak latencies (IPL) of the waves I-III of the BAEP and the wave IV (N2) of the fVEP between the three groups. Mean latency of the wave V and mean IPL of the waves I-V and the waves III-V were significantly different between the three groups. The kwashiorkor group had significantly longer mean latency of the wave V than the marasmus group on the right ear and the control group on the both of the ears. The kwashiorkor group had significantly longer mean IPL of the waves I-V than the marasmus group on the right ear and than the control group on the left ear. The kwashiorkor group had also significantly longer mean IPL of the waves III-V than the control group on the left. CONCLUSIONS: The BAEP and fVEP are non-invasive electrophysiologic methods reflecting the integrity or disruption of the central neurologic pathways. The present results confirm the disruption of the central nervous system with the BAEP in children with protein-energy malnutrition, especially in kwashiorkor patients.

Synergistic effects of citicoline and MK-801 in temporary experimental focal ischemia in rats.

BACKGROUND AND PURPOSE: Citicoline, a naturally occurring precursor of phosphatidylcholine, is neuroprotective and is currently being assessed in clinical trials. To evaluate potential synergistic neuroprotective effects of prolonged citicoline treatment and early N-methyl-D-aspartate (NMDA) antagonist therapy, suboptimal treatment regimens of citicoline and MK-801 were tested alone and in combination in a rat model of temporary focal ischemia. METHODS: Four groups of Sprague-Dawley rats (n = 12 per group) underwent 90 minutes of temporary middle cerebral artery occlusion (MCAO) with the suture model. Animals were randomly and blindly assigned to one of four treatment groups: (1) saline, vehicle; (2) MK-801, 0.5 mg/kg IV bolus at 60 minutes after MCAO followed by saline 1 mL/kg IP daily for 7 days; (3) saline IV at 60 minutes after MCAO followed by citicoline 250 mg/kg IP daily for 7 days; or (4) both MK-801 and citicoline (daily for 7 days) active treatment. Triphenyltetrazolium chloride staining was used to assess postmortem infarct volume. Neurological scores were determined daily. RESULTS: Premature mortality between days 2 and 4 was 33.3% in group 1, 41.7% in groups 2 and 3, and 25.0% in group 4. Mean corrected infarct volume was significantly reduced in group 4 compared with the others (175.2 +/- 89.3 mm3 in group 1, 179.1 +/- 78.5 mm3 in group 2, 163.9 +/- 73.7 mm3 in group 3, and 84.7 +/- 56.8 mm3 in group 4 [P < .02, ANOVA and P < .05, Scheffé's test for group 1 versus group 4]). Mean infarct volume in animals dying prematurely was significantly (P < .05, Student's t test) larger in group 1 than those surviving for 7 days (247.2 +/- 89.5 versus 139.2 +/- 68.2 mm3), but there was no significant difference in infarct volume in groups 2, 3, and 4 between animals dying prematurely and those surviving for 7 days. CONCLUSIONS: These results demonstrate synergistic neuroprotective effects of citicoline and an NMDA antagonist in temporary experimental focal ischemia.

Acute ischemic stroke therapy. A clinical overview.

Acute ischemic stroke therapy has two basic therapies, dissolving the intravascular occlusion by thrombolytic therapy and protecting the brain from the harmfull cellular, and metabolic consequences ofischemic injury by neuroprotective therapy. It seems most likely that the methods that will be used to treat the acute ischemic stroke patient will be multiple, likely a combination of thrombolytic therapy for early reperfusion and neuroprotective therapy for maintaining vitality. In the last decade, a number of advances in the field of imaging and pharmacology have been made which should provide meaningful improvement for the management of acute ischemic stroke patients in the near future. This update summarizes recent clinical trials and emphasizes the question of risk versus benefit for the acute ischemic stroke therapies being developed.