We hypothesized that the brain-protective effect of hyperbaric oxygen (HBO) preconditioning in a transient global cerebral ischemia rat model is mediated by the inhibition of early apoptosis.One hundred ten male Sprague Dawley (SD) rats (300-350 g body weight) were allocated to the sham group and three other groups with 10 minutes of four-vessel occlusion, untreated or preconditioned with either 3 or 5 hyperbaric oxygenations. HBO preconditioning improved neurobehavioral scores and reduced mortality, decreased ischemic cell change, reduced the number of early apoptotic cells and hampered a conversion of early to late apoptotic alterations. HBO preconditioning reduced the immunoreactivity of phosphorylated p38 in vulnerable neurons and increased the expression of brain derived neurotrophic factor (BDNF) in early stage post-ischemia. However, preconditioning with 3 HBO treatments proved less beneficial than with 5 HBO treatments.We conclude that HBO preconditioning may be neuroprotective by reducing early apoptosis and inhibition of the conversion of early to late apoptosis, possibly through an increase in brain BDNF level and the suppression of p38 activation.

Neurosurgical procedures can result in brain injury by various means including direct trauma, hemorrhage, retractor stretch, and electrocautery. This surgically-induced brain injury (SBI) can cause post-operative complications such as brain edema. By creating a mouse model of SBI, we tested whether NADPH oxidase, an important reactive oxygen species producing enzyme, is involved in SBI using transgenic mice lacking gp91 phox subunit of NADPH oxidase (gp91 phox KO) and apocynin, a specific inhibitor of NADPH oxidase. Neurological function and brain edema were evaluated at 24 hours post-SBI in gp91 phox KO and wild-type littermates grouped into SBI and shamsurgery groups. Alternatively, mice were grouped into vehicle-and apocynin-treated (5mg/kg, i.p. 30 minutes before SBI) groups. Oxidative stress indicated by lipid peroxidation (LPO) was measured at 3 and 24 hours post SBI. The gp91 phox KO mice, but not the apocynin-treated mice showed significantly improved neurological scores. Brain edema was observed in both gp91 phox KO and wild-type groups after SBI; however, there was no significant difference between these two groups. Brain edema was also not affected by apocynin-pretreatment. LPO levels were significantly higher in SBI group in both gp91 phox KO and wild-type groups as compared to sham group. A trend, although without statistical significance, was noted towards attenuation of LPO in the gp91 phox KO animals as compared to wild-type group. LPO levels were significantly attenuated at 3 hours post-SBI by apocynin pretreatment but not at 24 hours post-SBI. These results suggest that chronic and acute inhibition of NADPH oxidase activity does not reduce brain edema after SBI. Long-term inhibition of NADPH oxidase, however improves neurological functions after SBI.

Testing new concepts of vasospasm etiology will require re-evaluation of in vivo models of CVS. The updated knowledge about their advantages and limitations is necessary for effective design in future studies of cerebral vasospasm after SAH.

An unavoidable complication of space travel is exposure to high-charge, high-energy (HZE) particles. In animal studies, exposure of the CNS to HZE-particle radiation leads to neurological alterations similar to those seen in aging or Alzheimer's disease. In this study we examined whether HZE-particle radiation accelerated the age-related neuronal dysfunction that was previously described in transgenic mice overexpressing human amyloid precursor protein (APP). These APP23 transgenic mice exhibit age-related behavioral abnormalities and deficits in synaptic transmission. We exposed 7-week-old APP23 transgenic males to brain-only (56)Fe-particle radiation (600 MeV/nucleon; 1, 2, 4 Gy) and recorded synaptic transmission in hippocampal slices at 2, 6, 9, 14 and 18-24 months. We stimulated Schaeffer collaterals and recorded field excitatory postsynaptic potentials (fEPSP) and population spikes (PS) in CA1 neurons. Radiation accelerated the onset of age-related fEPSP decrements recorded at the PS threshold from 14 months of age to 9 months and reduced synaptic efficacy. At 9 months, radiation also reduced PS amplitudes. At 6 months, we observed a temporary deficit in paired-pulse inhibition of the PS at 2 Gy. Radiation did not significantly affect survival of APP23 transgenic mice. We conclude that irradiation of the brain with HZE particles accelerates Alzheimer's disease-related neurological deficits.

356Spontaneous subarachnoid hemorrhage (SAH) represents 5-7% of all strokes, 1,2 and SAH-related mortality reaches 50%. [3][4][5] Acute cerebral ischemia and subsequent injury are major causes of morbidity after SAH. 3,6 Several studies, including investigations in superoxide dismutase (SOD) transgenic mice, showed that superoxide and other reactive oxygen species (ROS) largely contribute to the early brain injury after SAH. [7][8][9][10][11] NADPH oxidase has been primarily described as responsible for superoxide production in phagocytes.12 Superoxide is generated on the membrane component gp91 phox , [13][14][15] which is expressed in all regions of the brain, with prominent localizations in the hippocampus, cortex, amygdale, striatum, and thalamus. 16ABSTRACT: Background: Oxidative stress largely contributes to early brain injury after subarachnoid hemorrhage (SAH). One of the major sources of reactive oxygen species is NADPH oxidase, upregulated after SAH. We hypothesized that NADPH oxidase-induced oxidative stress plays a major causative role in early brain injury after SAH. Methods: Using gp91 phox knockout (ko) and wild-type (wt) mice, we studied early brain injury in the endovascular perforation model of SAH. Mortality rate, cerebral edema, oxidative stress, and superoxide production were measured at 24 h after SAH. Neurological evaluation was done at 23 h after SAH surgery. Results: Genotyping confirmed the existence of a nonfunctional gp91 phox gene in the ko mice. CBF measurements did not show differences in SAH-induced acute ischemia between ko and wt mice. SAH caused a significant increase of water content in the ipsilateral hemisphere as well as an increase of Malondialdehyde (MDA) levels and superoxide production. There were no significant differences in post-SAH mortality rate, brain water content and the intensity of the oxidative stress between knockout and wild type groups of mice. Conclusions: Our results suggest that gp91 phox is not critically important to the early brain injury after SAH. An adaptive compensatory mechanism for free radical production in knockout mice is discussed.RÉSUMÉ: Le stress oxydatif après une hémorragie sous-arachnoïdienne chez les souris knock-out gp91-phox. Contexte : Le stress oxydatif contribue de façon importante aux lésions précoces dues à une hémorragie sous-arachnoïdienne (HSA). La NADPH oxydase est une des sources majeures de dérivés réactifs de l'oxygène qui est régulée à la hausse après une HSA. Nous avons émis l'hypothèse que le stress oxydatif induit par la NADPH oxydase est une cause majeure de dommage cérébral après une HSA. Méthodes : Nous avons étudié les dommages cérébraux précoces chez le modèle de HSA par perforation endovasculaire chez des souris de phénotype sauvage (ps) et des souris knock-out (ko) gp91-phox. Le taux de mortalité, l'?dème cérébral, le stress oxydatif et la production de superoxyde ont été mesurés 24 heures après l'HSA. L'évaluation neurologique était faite 23 heures après la chirurgie. Résultats : Le génotypage a confirmé l'ex...