The overall objective of this research component is to investigate the high-energy biochemical mechanisms whereby the perinatal brain is damaged by hypoxia-ischemia and how brain injury can be prevented or reduced through specific modalities of therapy.
Specific Aims i nclude: 1) to characterize the earliest alterations in high-energy phosphate reserves which occur during perinatal cerebral hypoxia-ischemia and to correlate these changes with perturbations in cerebral energy utilization, cerebral glucose utilization, glutamate and nitric oxide neurotoxicity, and intracellular calcium accumulation; 2) to correlate the concentrations in cerebral high-energy phosphate reserves and the changes which occur during hypoxia-ischemia using 31P magnetic resonance (MR) spectroscopic methods and enzymatic, fluorometric techniques; 3) to characterize the secondary (delayed) energy failure which occurs during recovery from perinatal cerebral hypoxia-ischemia and to correlate the alterations with the presence and severity of hypoxia-ischemic brain damage; 4) to ascertain underlying biochemical mechanisms whereby the glucocorticosteroid, dexamethasone, protects the perinatal brain from hypoxic-ischemic damage; 5) to determine the protective influence of magnesium sulfate on perinatal hypoxic-ischemic brain damage and, if so, to ascertain its mechanism of action; and 6) to investigate further the presence and extend of alterations in diffusion-weighted and T2-weighted imaging during recovery from perinatal cerebral hypoxia-ischemia and to correlate any changes with the nature and extent of cerebral edema and associated neuropathologic alterations. Seven-days postnatal rats will undergo unilateral cerebral hypoxia-ischemia, during and following which the animals will undergo those procedures necessary to obtain sequential 31P and 1H NMR spectra which will allow for measurements of the alterations in high-energy phosphate reserves and other metabolites which result from the insult. Other animals will undergo MR imaging at specific intervals following cerebral hypoxia-ischemia. Other experiments will elucidate the neuroprotective effect of dexamethasone, magnesium sulfate, and L-NAME on hypoxic-ischemic brain damage in the developing rat. Analytic procedures will include sequential measures with NMR spectroscopy as well as brain tissue analysis of high-energy phosphate reserves and other metabolites using enzymatic, fluorometric techniques.
|Leroy, Claire; Pierre, Karin; Simpson, Ian A et al. (2011) Temporal changes in mRNA expression of the brain nutrient transporters in the lithium-pilocarpine model of epilepsy in the immature and adult rat. Neurobiol Dis 43:588-97|
|Sen, Ellora; Basu, Anirban; Willing, Lisa B et al. (2011) Pre-conditioning induces the precocious differentiation of neonatal astrocytes to enhance their neuroprotective properties. ASN Neuro 3:e00062|
|Simpson, Ian A; Carruthers, Anthony; Vannucci, Susan J (2007) Supply and demand in cerebral energy metabolism: the role of nutrient transporters. J Cereb Blood Flow Metab 27:1766-91|
|Jin, Yuxuan; Silverman, Ann-Judith; Vannucci, Susan J (2007) Mast cell stabilization limits hypoxic-ischemic brain damage in the immature rat. Dev Neurosci 29:373-84|
|Kremlev, Sergey G; Roberts, Rebecca L; Palmer, Charles (2007) Minocycline modulates chemokine receptors but not interleukin-10 mRNA expression in hypoxic-ischemic neonatal rat brain. J Neurosci Res 85:2450-9|
|Zhang, X; Surguladze, N; Slagle-Webb, B et al. (2006) Cellular iron status influences the functional relationship between microglia and oligodendrocytes. Glia 54:795-804|
|Nehlig, Astrid; Rudolf, Gabrielle; Leroy, Claire et al. (2006) Pentylenetetrazol-induced status epilepticus up-regulates the expression of glucose transporter mRNAs but not proteins in the immature rat brain. Brain Res 1082:32-42|
|Hurn, Patricia D; Vannucci, Susan J; Hagberg, Henrik (2005) Adult or perinatal brain injury: does sex matter? Stroke 36:193-5|
|Kremlev, Sergey G; Palmer, Charles (2005) Interleukin-10 inhibits endotoxin-induced pro-inflammatory cytokines in microglial cell cultures. J Neuroimmunol 162:71-80|
|Basu, Anirban; Lazovic, Jelena; Krady, J Kyle et al. (2005) Interleukin-1 and the interleukin-1 type 1 receptor are essential for the progressive neurodegeneration that ensues subsequent to a mild hypoxic/ischemic injury. J Cereb Blood Flow Metab 25:17-29|
Showing the most recent 10 out of 55 publications