Experimental neurology
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Experimental neurology · Jan 2000
Neuronal subclass-selective loss of pyruvate dehydrogenase immunoreactivity following canine cardiac arrest and resuscitation.
Chronic impairment of aerobic energy metabolism accompanies global cerebral ischemia and reperfusion and likely contributes to delayed neuronal cell death. Reperfusion-dependent inhibition of pyruvate dehydrogenase complex (PDHC) enzyme activity has been described and proposed to be at least partially responsible for this metabolic abnormality. This study tested the hypothesis that global cerebral ischemia and reperfusion results in the loss of pyruvate dehydrogenase immunoreactivity and that such loss is associated with selective neuronal vulnerability to transient ischemia. ⋯ A significant decrease in immunoreactivity was observed in frontal cortex homogenates from both 2 and 24 h reperfused animals compared to samples from nonischemic control animals. These results were supported by confocal microscopic immunohistochemical determinations of pyruvate dehydrogenase immunoreactivity in the neuronal cell bodies located within different layers of the frontal cortex. Loss of immunoreactivity was greatest for pyramidal neurons located in layer V compared to neurons in layers IIIc/IV, which correlates with a greater vulnerability of layer V neurons to delayed death caused by transient global cerebral ischemia.
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Experimental neurology · Dec 1999
Effects of the serotonin synthesis inhibitor p-CPA on the expression of the crossed phrenic phenomenon 4 h following C2 spinal cord hemisection.
The present study assesses the effects of para-chlorophenylalanine (p-CPA), a serotonin-depleting drug, on the recovery of respiratory-related activity in the phrenic nerve induced by asphyxia 4 h following ipsilateral C2 hemisection in young adult rats. HPLC analysis was used to quantify levels of serotonin (5-HT), dopamine (DA), norepinephrine, and the 5-HT metabolite, 5-hydroxyindoleacetic acid, in the C4 segment of the spinal cord, all of which were significantly lower in p-CPA-treated hemisected rats compared to hemisected controls receiving saline. Hemisection alone was found to significantly increase 5-HT levels and significantly decrease DA levels compared to normal controls. ⋯ In addition, saline controls demonstrated significant increases in mean respiratory frequency and mean amplitude of contralateral phrenic nerve activity during asphyxia, compared to normocapnia. However, p-CPA-treated rats did not express significant differences in either mean respiratory frequency or mean amplitude of integrated respiratory wave-forms during asphyxia, compared to normocapnia. The results suggest that p-CPA treatment attenuates the recovery of respiratory-related activity in the phrenic nerve 4 h following ipsilateral C2 hemisection and attenuates asphyxia-induced increases in respiratory frequency and respiratory burst amplitude recorded from the contralateral phrenic nerve.
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Experimental neurology · Dec 1999
Effects of serotonin on crossed phrenic nerve activity in cervical spinal cord hemisected rats.
The present study investigates the effect of 5-hydroxytryptophan (5-HTP), a serotonin precursor, on crossed phrenic nerve activity (CPNA) in rats subjected to a left C2 spinal cord hemisection. Electrophysiological experiments were conducted on anesthetized, vagotomized, paralyzed, and artificially ventilated rats to assess phrenic nerve activity. ⋯ Specifically, in a group of eight animals, application of 5-HTP at 0.5, 1.0, and 2.0 mg/kg significantly increased CPNA by 102.2+/-18.5%, 200.8+/-58.1%, and 615.0+/-356.9% compared with predrug control values, respectively. 5-HTP-induced increases in CPNA were reversed by methysergide (2-6 mg/kg, i.v.), a serotonin receptor antagonist. The results suggest that serotonin is involved in the modulation of crossed phrenic nerve activity following spinal cord injury.
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Experimental neurology · Nov 1999
Cyclosporin A attenuates acute mitochondrial dysfunction following traumatic brain injury.
Experimental traumatic brain injury (TBI) results in a rapid and significant necrosis of cortical tissue at the site of injury. In the ensuring hours and days, secondary injury exacerbates the primary damage, resulting in significant neurological dysfunction. Recent reports from our lab and others have demonstrated that the immunosuppressant cyclosporin A (CsA) is neuroprotective following TBI. ⋯ Similarly, synaptosomes isolated from CsA-treated animals demonstrate a significant increase in mitochondria membrane potential, accompanied by lower levels of intramitochondrial Ca2+ and reactive oxygen species production than seen in vehicle-treated animals. These results suggest that the neuroprotective properties of CsA are mediated through modulation of the MPTP and maintenance of mitochondria homeostasis. Amelioration of cortical damage with CsA indicates that pharmacological therapies can be devised which will significantly alter neurological outcome after injury.
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Experimental neurology · Nov 1999
Comparative StudyEffects of vaginal birth versus caesarean section birth with general anesthesia on blood gases and brain energy metabolism in neonatal rats.
Using a rat model, several laboratories have demonstrated long-term effects of Caesarean section (C-section) birth or of global hypoxia during C-section birth on a variety of central nervous system (CNS) parameters. These studies used C-section delivery from rapidly decapitated dams, to avoid confounding anesthetic effects, or from dams anesthetized with halothane or ether under unspecified conditions. Systemic oxygenation or cerebral energy metabolites in the pups at birth have not been systematically measured in this model. ⋯ In conclusion, rat neonates show minimal signs of systemic or CNS hypoxia following C-section birth under 2.5% isoflurane with N2O. However, there is a rather narrow window of isoflurane concentrations which produces effective maternal anesthesia without producing respiratory compromise in the neonate. Thus the results indicate that the level of maternal anesthesia employed is an important factor influencing neonatal systemic and CNS oxygenation during C-section birth.