Biomedical subjects

Vadim S Ten

Publications and source records attributed to Vadim S Ten.

6 recordsLinked to original sources

PubMed2006

Reoxygenation with 100% oxygen versus room air: late neuroanatomical and neurofunctional outcome in neonatal mice with hypoxic-ischemic brain injury.

Study investigated neuroutcome in mice subjected at 7-8 d of life to hypoxic-ischemic brain injury (HI) followed by 30 min of reoxygenation with 100% O(2) (Re-O(2)) or room air (Re-Air). At 24 h of recovery, mouse reflexes were tested. At 7 wks after HI spatial orientation and memory were assessed in the same mice. Mortality rate was recorded at 24 h and at 7 wks of recovery. In separate cohort of mice, changes in cerebral blood flow (CBF) during HI-insult and reoxygenation were recorded. Re-O(2)versus Re-Air mice exhibited significantly delayed geotaxis reflex. Adult Re-O(2)versus Re-Air mice exhibited significantly better spatial learning and orientation with strong tendency toward better preserved memory. Histopathology revealed significantly less hippocampal atrophy in Re-O(2)versus Re-Air mice. Following a hypoxia-induced hypoperfusion, Re-O(2) re-established CBF in the ipsilateral side to the prehypoxic level significantly faster than Re-Air. The mortality was higher among Re-O2 versus Re-Air mice, although, it did not reach statistical significance. Re-O(2)versus Re-Air restores CBF significantly faster and results in better late neuroutcome. However, greater early motor deficit and higher mortality rate among Re-O(2)versus Re-Air mice suggest that Re-O(2) may be deleterious at the early stage of recovery.

Air↗

PubMed2006

Temporal pattern of C1q deposition after transient focal cerebral ischemia.

Recent studies have focused on elucidating the contribution of individual complement proteins to post-ischemic cellular injury. As the timing of complement activation and deposition after cerebral ischemia is not well understood, our study investigates the temporal pattern of C1q accumulation after experimental murine stroke. Brains were harvested from mice subjected to transient focal cerebral ischemia at 3, 6, 12, and 24 hr post reperfusion. Western blotting and light microscopy were employed to determine the temporal course of C1q protein accumulation and correlate this sequence with infarct evolution observed with TTC staining. Confocal microscopy was utilized to further characterize the cellular localization and characteristics of C1q deposition. Western Blot analysis showed that C1q protein begins to accumulate in the ischemic hemisphere between 3 and 6 hr post-ischemia. Light microscopy confirmed these findings, showing concurrent C1q protein staining of neurons. Confocal microscopy demonstrated co-localization of C1q protein with neuronal cell bodies as well as necrotic cellular debris. These experiments demonstrate the accumulation of C1q protein on neurons during the period of greatest infarct evolution. This data provides information regarding the optimal time window during which a potentially neuroprotective anti-C1q strategy is most likely to achieve therapeutic success.

Animals↗

PubMed2005

C1q-deficiency is neuroprotective against hypoxic-ischemic brain injury in neonatal mice.

BACKGROUND AND PURPOSE: This study was undertaken to determine whether the initial component of the classical complement (C) activation pathway contributes to hypoxic-ischemic brain injury in neonatal mice. METHODS: Hypoxia-ischemia (HI) was produced in C1q(-/-) and wild-type (WT) neonatal mice. At 24 hours after HI, neonatal mouse reflex performance and cerebral infarct volume were assessed. Long-term outcomes were measured by water-maze performance and degree of cerebral atrophy at 7 to 8 weeks after HI. Activation of circulating neutrophils, and C1q, C3, and neutrophil deposition in brains were examined. RESULTS: C1q(-/-) mice were significantly protected against HI (mean+/-SE infarct volume in C1q(-/-) mice=17.3+/-5.5% versus 53.6+/-6.8% in WT mice; P<0.0001) and exhibited significantly less neurofunctional deficit compared with WT mice. Immunostaining revealed significantly greater deposition of C3 (and C1q) as well as granulocytes in the infarcted brains in WT mice compared with C1q(-/-) animals. Activation of circulating leukocytes was significantly decreased in C1q(-/-) mice compared with WT mice, which correlated strongly (r=0.7) with cerebral infarct volumes. CONCLUSIONS: Cerebral deposition of C1q and C3 after hypoxic-ischemic insult is associated with significantly greater neurologic damage in WT mice compared with C1q(-/-) mice, providing strong evidence that the classical C pathway contributes to the hypoxic-ischemic brain injury. Significantly decreased activation of circulating neutrophils associated with diminished local accumulation and attenuation of brain injury in C1q(-/-) mice suggests a potential cellular mechanism by which C1q mediates neurodegeneration in HI.

Animals↗

PubMed2004

Late measures of brain injury after neonatal hypoxia-ischemia in mice.

BACKGROUND AND PURPOSE: This work was undertaken to determine to what degree long-term neurofunctional outcome of neonatal hypoxic-ischemic (HI) brain injury in mice correlates with anatomical extent of cerebral damage assessed by magnetic resonance imaging (MRI) and histopathology. METHODS: On postnatal day 7, mice were subjected to HI. At 7 to 9 weeks after HI neurofunctional outcome was assessed by water-maze, rota-rod, and open-field test performance, followed by cerebral MRI and histopathology evaluation. RESULTS: At 10 weeks after HI, MRI revealed ipsilateral brain atrophy alone or with porencephalic cyst formation and contralateral ventriculomegaly. Adult HI-affected mice, especially those that developed a porencephalic cyst, demonstrated significant neurofunctional deficit compared with age-matched naïve mice. HI-affected mice with ipsilateral cerebral atrophy but without porencephaly demonstrated no or an intermediate level of neurofunctional deficit. Neurobehavioral assessment of mice subjected to HI insult revealed a strong correlation between degree of brain injury and functional neurohandicap. CONCLUSIONS: This is the first study to demonstrate that long-term neurofunctional outcome in mice after a neonatal HI correlates tightly with anatomical pattern/extent of cerebral damage, defined by MRI and histopathology.

Animals↗

PubMed2003

Brain injury and neurofunctional deficit in neonatal mice with hypoxic-ischemic encephalopathy.

Birth asphyxia accounts for the majority of developmental motor and cognitive deficits. Studies were undertaken to develop a reproducible murine model of perinatal hypoxic-ischemic encephalopathy (HIE) which would permit both anatomic and neurofunctional quantification of injury. Short-term neurofunctional outcomes consisted of three developmental reflexes (righting, cliff aversion and geotaxis) assessed in 7-day-old mouse pups 24 h after unilateral carotid artery ligation followed by inhalation of 8% oxygen. Cerebral infarct volume was dependent on duration of hypoxia, being approximately 2.5-fold greater with longer (60 min) versus shorter (30 min) hypoxia exposure (P=0.001). All three sensorimotor neonatal reflexes assessed at 24 h after HIE injury correlated significantly with long-term neurofunction evaluated using a water-maze test of navigational learning and memory assessed 8 weeks later in the same animals. Cerebral atrophy, a delayed consequence of HIE in this model, also correlated strongly with water-maze performance (r=0.86, P=0.002). These data demonstrate for the first time that murine neonatal sensorimotor reflex performance can be rigorously quantified in the acute phase of perinatal HIE and has strong predictive value not only for anatomic extent of cerebral injury, but also for long-term neurofunctional outcome.

Animals↗

PubMed2002

Endothelial response to hypoxia: physiologic adaptation and pathologic dysfunction.

When subjected to a period of oxygen deprivation, endothelial cells exhibit a characteristic pattern of responses that can be considered either adaptive or pathologic, depending on the circumstances. In this review, the molecular basis for these responses is detailed. Hypoxia shifts the endothelial phenotype towards one in which anticoagulant properties are diminished, permeability and leukoadhesivity are increased, and proinflammatory features dominate the endovascular milieu. Of all the different points of intersection between the coagulation and inflammatory axes in the vasculature, perhaps most fundamentally, hypoxia alters several key transcriptional factors, including early growth response gene 1 (Egr1) and hypoxia-inducible factor (HIF) 1, which coordinate separate programs of gene activation. The preponderance of forces in the hypoxic endovascular environment, perhaps designed as an evolutionary adaptation to oxygen deprivation, can trigger severe, pathologic, clinical consequences in the setting of tissue ischemia.

Adaptation, Physiological↗