Acute hypoxia-ischemia results in hydrogen peroxide accumulation in neonatal but not adult mouse brain

The neonatal brain responds differently to hypoxic-ischemic injury and may be more vulnerable than the mature brain due to a greater susceptibility to oxidative stress. As a measure of oxidative stress, the immature brain should accumulate more hydrogen peroxide (H2O2) than the mature brain after a similar hypoxic-ischemic insult. To test this hypothesis, H2O2 accumulation was measured in postnatal day 7 (P7, neonatal) and P42 (adult) CD1 mouse brain regionally after inducing HI by carotid ligation followed by systemic hypoxia. H2O2 accumulation was quantified at 2, 12, 24, and 120 h after HI using the aminotriazole (AT)-mediated inhibition of catalase spectrophotometric method. Histologic injury was determined by an established scoring system, and infarction volume was determined. P7 and P42 animals were subjected to different durations of hypoxia to create a similar degree of brain injury. Despite similar injury, significantly less H2O2 accumulated in P42 mouse cortex compared with P7 at 2, 12, and 24 h after HI. In addition, less H2O2 accumulated in P42 mouse hippocampus compared with P7 hippocampus at 2 h. Since immature neurons are more vulnerable to the toxic effects of H2O2 than mature neurons, this increased accumulation in the immature brain may explain why the neonatal brain may be more devastated, even after a milder degree of acute hypoxic-ischemic injury.     

Presentation of type I Chiari malformation after head trauma

An unusual case of Type I Chiari malformation that became symptomatic after closed head injury is reported. The patient manifested transient upper extremity weakness, persistent lower cranial nerve dysfunction, and cerebellar signs that slowly resolved. Magnetic resonance images showed tonsillar ectopia but no displacement of the brain stem or syringomyelia. Type I Chiari malformation should be included in the differential diagnosis of patients who present with upper extremity weakness, lower cranial nerve palsies, or cerebellar signs after trauma.     

Cerebral palsy: MR findings in 40 patients.

PURPOSE: We used MR to retrospectively analyze the brains of patients suffering from cerebral palsy, our aim being to determine MR's role in the assessment of brain damage and the relationship of pre-, peri-, and post-natal events to cerebral palsy. METHODS: Forty patients (aged 1 month to 41 years) underwent MR scanning and findings were correlated with clinical histories in all cases. RESULTS: Review of MR scans of 11 patients who had been born prematurely revealed findings of periventricular white matter damage, indicative of hypoxic-ischemic brain injury (82%), the chronology of which was difficult to determine. Among 29 patients who had been born at term, three major patterns emerged: (1), gyral anomalies, suggestive of polymicrogyria, consistent with mid-second trimester injury; (2), isolated periventricular leukomalacia reflecting late second- or early third-trimester injury; and (3), watershed cortical or deep gray nuclear damage, consistent with late third-trimester, perinatal or postnatal injury. In 16 (55%) of 29 patients born at term, MR findings of intrauterine brain damage were observed; in over half of these cases MR revealed developmental anomalies, which is nearly twice the rate reported in prior studies employing CT. CONCLUSIONS: Our results support a growing consensus that cerebral palsy in term infants is often the result of prenatal factors, and less commonly related to the perinatal period.     

Protecting Neurons

Summary:  Brain injury evolves over time, often taking days or even weeks to fully develop. It is a dynamic process that involves immediate oxidative stress and excitotoxicity followed by inflammation and preprogrammed cell death. This article presents a brief overview of mechanisms of neuroprotection in the developing brain. Although the focus is on ischemic injury, the conclusions drawn apply to any type of brain insult—epileptic seizures, trauma, or ischemia.
  Strategies of neuroprotection include salvaging neurons through the use of targeted pharmacotherapies, protecting neurons through preconditioning, and repairing neurons by enhancing neurogenesis. Drug therapies that dampen the impact of immediate and downstream postinjury events are only modestly effective in protecting the brain from ischemic injury. In experimental models, complete or true protection can be achieved only through preconditioning, a process during which an animal develops tolerance to an otherwise lethal stressor. Although of no clinical use, preconditioning models have provided valuable insight into how repair systems work in the brain. Cumulative evidence indicates that the same genes that are upregulated during preconditioning, those mediating true protection, are also upregulated during injury and repair. Specifically, hypoxic preconditioning and hypoxic-ischemic insult have been shown to induce hypoxia inducible factor-1 (HIF-1) and its target survival genes, vascular endothelial growth factor (VEGF), and erythropoietin (Epo) in rodents. Of particular interest is the upregulation of Epo, a growth factor that may have therapeutic potential in the treatment of ischemic stroke. At this time, however, the postinjury enhancement of neurogenesis appears to offer the best hope for long-lasting functional recovery following brain injury.     

Involvement of the pontomedullary corticospinal tracts: a useful finding in the diagnosis of X-linked adrenoleukodystrophy.

PURPOSETo determine whether pontomedullary corticospinal tract involvement is a common and specific finding of adrenoleukodystrophy on MR images.METHODSMR images of 10 patients with biochemically proved adrenoleukodystrophy who were examined during the last 6 years were reviewed retrospectively to determine the frequency of corticospinal tract involvement in the medulla, pons, mesencephalon, internal capsules, and corona radiata. MR images of 10 patients with other leukodystrophies (three with Krabbe disease, two with Alexander disease, two with metachromatic leukodystrophy, two with Pelizaeus-Merzbacher disease, and one with Canavan disease) were reviewed with specific attention to the pontomedullary corticospinal tracts.RESULTSMedullary and pontine corticospinal tract involvement was present in eight of the 10 patients with adrenoleukodystrophy. Mesencephalic and internal capsular involvement was present in three patients. The coronal radiata portion of the corticospinal tracts was not involved in any of the 10 patients. No pontomedullary corticospinal tract involvement was identified in any of the 10 patients with other leukodystrophies. The difference in the frequency of pontomedullary corticospinal tract involvement between the two groups was highly significant.CONCLUSIONPontomedullary corticospinal tract involvement is a common finding in adrenoleukodystrophy and is unusual in other leukodystrophies. Awareness of this finding can facilitate the radiologic diagnosis of this disease and may expedite management of affected patients.