Cerebral Palsy

Primary objective: To examine the hospitalization costs and discharge outcomes of US children with TBI and to evaluate a severity measure, the predictive mortality likelihood level. Research design: Data from the 2006 Healthcare Cost and Utilization Project Kids’ Inpatient Database (KID) were used to report the national estimates and characteristics of TBI-associated hospitalizations among US children </=20 years of age. The percentage of children with TBI caused by motor vehicle crashes (MVC) and falls was calculated according to the predictive mortality likelihood levels (PMLL), death in hospital and discharge into long-term rehabilitation facilities. Associations with the PMLL, discharge outcomes and average hospital charges were examined. Results: In 2006, there were an estimated 58 900 TBI-associated hospitalizations among US children, accounting for $2.56 billion in hospital charges. MVCs caused 38.9% and falls caused 21.2% of TBI hospitalizations. The PMLL was strongly associated with TBI type, length of hospital stay, hospital charges and discharge disposition. About 4% of children with fall or MVC related TBIs died in hospital and 9% were discharged into long-term facilities. Conclusion: The PMLL may provide a useful tool to assess characteristics and treatment outcomes of hospitalized TBI children, but more research is still needed.

A novel bromide salt of the antidepressant bupropion (bupropion HBr) has recently been developed and approved for use in the United States. Given previous use of bromides to treat seizures, and that the existing chloride salt of bupropion (HCl) can cause seizures, it is important to determine if the HBr salt may be less likely to cause seizures than the HCl salt. In the present animal studies this was evaluated by means of quantified electroencephalogram (EEG), observation, and the rotarod test in mice and rats. Both bupropion salts were tested at increasing equimolar doses administered intraperitoneally. The results in mice showed that bupropion HCl 125 mg/kg induced a significantly higher ten-fold increase in the mean number of cortical EEG seizures compared to bupropion HBr (7.50 +/- 2.56 vs 0.75 +/- 0.96; p = 0.045), but neither drug caused any brain injuries. In rats bupropion HBr 100 mg/kg induced single EEG seizure activity in the cortical and hippocampal (depth) electrodes and in significantly (p < 0.05) fewer rats (44%) compared to bupropion HCl, which induced 1 to 4 convulsions per rat in all rats (100%) dosed. The total duration of cortical seizures in bupropion HCl-treated rats was significantly longer than the corresponding values obtained in bupropion HBr-treated rats (424.6 seconds vs 124.5 seconds respectively, p < 0.05). Bupropion HCl consistently induced more severe convulsions at each dose level compared to bupropion HBr. Both treatments demonstrated a similar dose-dependent impairment of rotarod performance in mice. In conclusion, these findings suggest that bupropion HBr may have a significantly lower potential to induce seizures in mice and rats, particularly at higher doses, compared to bupropion HCl. Determination of this potential clinical advantage will require human studies. If confirmed by such studies, it is likely that this potential beneficial clinical benefit would be due to the presence of the bromide salt given the long history of the use of bromide to treat seizure disorders.

Melatonin (n-acetyl-5-methoxy-tryptamine), a naturally occurring indole produced mainly by the pineal gland, is a well known antioxidant. Stroke (cerebral ischemia) is the second leading cause of death worldwide. To date, however, effective and safe treatment for stroke remains unavailable. Melatonin is both lipid- and water-soluble and readily crosses the blood-brain barrier (BBB). Increasing evidence has shown that, in animal stroke models, administering melatonin significantly reduces infarct volume, edema, and oxidative damage and improves electrophysiological and behavioral performance. Here, we reviewed studies that assess effects of melatonin on cerebral ischemia in acute, sub-acute, and chronic stages. In addition to its potent antioxidant properties, melatonin exerts antiapoptotic, antiexcitotoxic, anti-inflammatory effects and promotes mitochondrial functions in animals with cerebral ischemia. Given that melatonin shows almost no toxicity to humans and possesses multifaceted protective capacity against cerebral ischemia, it is valuable to consider using melatonin in clinical trials on patients suffering from stroke.

Repositioning microelectrodes post-implantation is emerging as a promising approach to achieve long-term reliability in single neuronal recordings. The main goal of this study was to (a) assess glial reaction in response to movement of microelectrodes in the brain post-implantation and (b) determine an optimal window of time post-implantation when movement of microelectrodes within the brain would result in minimal glial reaction. Eleven Sprague-Dawley rats were implanted with two microelectrodes each that could be moved in vivo post-implantation. Three cohorts were investigated: (1) microelectrode moved at day 2 (n = 4 animals), (2) microelectrode moved at day 14 (n = 5 animals) and (3) microelectrode moved at day 28 (n = 2 animals). Histological evaluation was performed in cohorts 1-3 at four-week post-movement (30 days, 42 days and 56 days post-implantation, respectively). In addition, five control animals were implanted with microelectrodes that were not moved. Control animals were implanted for (1) 30 days (n = 1), (2) 42 days (n = 2) and (3) 56 days (n = 2) prior to histological evaluation. Quantitative assessment of glial fibrillary acidic protein (GFAP) around the tip of the microelectrodes demonstrated that GFAP levels were similar around microelectrodes moved at day 2 when compared to the 30-day controls. However, GFAP expression levels around microelectrode tips that moved at day 14 and day 28 were significantly less than those around control microelectrodes implanted for 42 and 56 days, respectively. Therefore, we conclude that moving microelectrodes after implantation is a viable strategy that does not result in any additional damage to brain tissue. Further, moving the microelectrode downwards after 14 days of implantation may actually reduce the levels of GFAP expression around the tips of the microelectrodes in the long term.

Aneurysmal subarachnoid hemorrhage (aSAH) is one type of hemorrhagic stroke in humans. F(2)-isoprostanes (F(2)-IsoPs) and F(4)-neuroprostanes (F(4)-NPs), derived from arachidonic acid and docosahexaenoic acid (DHA), respectively, are specific markers of lipid peroxidation. We previously demonstrated that F(2)-IsoPs levels in cerebrospinal fluid (CSF) of aSAH patients positively correlated with poor clinical conditions. In this work, we refined F(4)-NPs analysis and investigated the role of potential oxidative damage to neurons in aSAH patients by detecting F(4)-NPs in CSF. [(2)H(4)]-15-F(2t)-IsoP, rather than [(18)O(2)]-17-F(4c)-NP or [(2)H(4)]-PGF(2alpha), was used as the internal standard for F(4)-NPs analysis. One problem of the use of [(18)O(2)]-17-F(4c)-NP was the potential interference resulted from F(2)-dihomo-IsoPs in CSF. CSF specimen of 15 aSAH patients for up to 10 days and that of 12 non-aSAH controls were analyzed. First-day, mean, and peak levels of F(4)-NPs in aSAH patients were all significantly higher than controls and correlated with Fisher Scale and three-month Glasgow Outcome Scale, but only mean levels of F(4)-NPs correlated with Hunt and Hess Grade. The results first demonstrate oxidative damage to DHA in brain tissue following aSAH and suggest that F(4)-NPs in CSF could be a better predictor for outcome of aSAH than F(2)-IsoPs at early time points.

Synaptic dysfunction has been associated with neuronal cell death following hypoxia. The lack of knowledge on the mechanisms underlying this dysfunction prompted us to investigate the morphological changes in the postsynaptic densities (PSDs) induced by hypoxia. The results presented here demonstrate that PSDs of the rat neostriatum are highly modified and ubiquitinated 6 months after induction of hypoxia in a model of perinatal asphyxia. Using both two dimensional (2D) and three dimensional (3D) electron microscopic analyses of synapses stained with ethanolic phosphotungstic acid (E-PTA), we observed an increment of PSD thickness dependent on the duration and severity of the hypoxic insult. The PSDs showed clear signs of damage and intense staining for ubiquitin. These morphological and molecular changes were effectively blocked by hypothermia treatment, one of the most effective strategies for hypoxia-induced brain injury available today. Our data suggest that synaptic dysfunction following hypoxia may be caused by long-term misfolding and aggregation of proteins in the PSD.

Hypoxia and reoxygenation set in motion a series of events, including blood-brain barrier breakdown. We examined the content and effect of platelet-activating factor (PAF), which was increased in the rat brain microvessel endothelial cells (RBMECs) during hypoxia and reoxygenation. MTT method was used to assay cell damage; ELISA analysis was used to estimate PAF release after hypoxia and reoxygenation injury; and RT-PCR and Western blotting method were used to assess gene and protein expression of inducible nitric-oxide synthase (iNOS) in RBMECs under PAF damage. PAF affected intracellular free Ca(2+) levels , increasing [Ca(2+)](i), which caused up-regulation of iNOS. We also examined the blood-brain barrier protective effect of XQ-1H, a novel ginkgolide B derivative. Pretreatment with XQ-1H (10muM and 3muM) for 24 h significantly antagonized PAF receptor and inhibited the increase in intracellular calcium concentration and the up-regulation of iNOS in response to PAF under hypoxia and reoxygenation in vitro.

STUDY OBJECTIVE: The primary intention of spiral computed tomography (SCT) in trauma patients is to identify significant injuries. However, unanticipated information is often discovered. We hypothesize that SCT often identifies clinically significant incidental findings in trauma patients. METHODS: This was a retrospective protocol chart review of consecutive adult trauma patients seen at a level I trauma center. A complete SCT was defined as computed tomography imaging of the head, cervical spine, chest, abdomen, and pelvis, thoracic, and lumbar spine. Incidental findings were classified into 2 categories: type 1, which requires urgent evaluation, and type 2, which requires informing the patient but does not mandate urgent follow-up. RESULTS: We reviewed 3246 patient charts and 3092 met inclusion criteria. Type 1 findings were reported in 990 (32.0%; 95% confidence interval [CI], 30.4%-33.7%) patients. Type 2 findings were found in 1274 (41.2%; 95% CI, 39.5%-42.9%) patients. Female sex (odds ratio, 1.38; 95% CI, 1.16-1.65) and older age (odds ratio, 2.61; 95% CI, 2.33-2.93) were independently associated with a higher prevalence of type 1 findings. There were 631 incidental findings concerning for neoplasm, which included 196 pulmonary nodules, 99 liver, 36 renal, 23 brain, and 11 breast masses. CONCLUSIONS: A significant number of trauma patients evaluated with SCT are diagnosed with potentially serious incidental findings. For long-term care and medicolegal concerns, physicians need to inform patients of these incidental findings and the need for further evaluation.

The Morris water maze is a standard paradigm for the testing of hippocampal function in laboratory animals. Virtual versions of the Morris water maze are now available and can be used to assess spatial learning and memory ability in both healthy and brain injured participants. To evaluate the importance of the hippocampus in spatial learning and memory, we tested five amnesic participants with selective hippocampal damage using a virtual water maze called the Arena Maze. The amnesic participants with hippocampal damage were impaired on the invisible platform (place) task that required them to use distal cues, but were able to navigate almost as well as comparison participants when the invisible platform was marked by a single proximal cue. These results not only confirm that the hippocampus plays a necessary role in human navigation in large-scale environments but also provides a new link between the mnemonic and navigational roles of the hippocampus. (c) 2009 Wiley-Liss, Inc.

In addition to data regarding its effects on the heart, brain and blood vessels, extensive evidence has emerged about the contribution of aldosterone to kidney damage. This has mainly been studied in the setting of experimental models of salt-sensitive hypertension but has been confirmed also in other animal models. The evidence is supported by a clear causal relationship between aldosterone infusion and development of kidney damage and its reversal after aldosterone blockade. Since 2001, clinical data have been obtained on the antiproteinuric effect of aldosterone antagonists added to ACE inhibitors or angiotensin II receptor blockers. Unfortunately, the long-term findings are still scanty, except for those obtained in two one-year studies. Altogether, this therapeutic approach appears relatively safe and effective; however, larger studies on patients with a wider range of chronic kidney disease severities and longer follow-up are needed to confirm it.