Brain research
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The morphological changes that occur during normal brain aging are not well understood. This study used modern stereology to assess the effects of age and gender on total numbers of astrocytes and microglia in the hippocampal formation in C57Bl/6NNIA (B6) mice. ⋯ We also report that on average female B6 mice have 25-40% more astrocytes and microglia in DG and CA1 regions than age-matched male C57Bl/6J mice. Since astrocytes and microglia are thought to be targets of gonadal hormones, the effects of sex hormones and reproductive aging may be responsible for these findings.
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Near-infrared spectroscopy (NIRS) enables continuous non-invasive quantification of blood and tissue oxygenation, and may be useful for quantification of cerebral blood volume (CBV) changes. In this study, changes in cerebral oxy- and deoxyhemoglobin were compared to corresponding changes in CBF and CBV as measured by positron emission tomography (PET). Furthermore, the results were compared using a physiological model of cerebral oxygenation. ⋯ Changes in CBV measured with both techniques were significantly correlated to CO(2) levels. However, deltaCBV(NIRS) was much smaller than deltaCBV(PET), and measured NIRS parameters smaller than those predicted from the model. It is concluded that while qualitatively correct, NIRS measurements of CBV should be used with caution when quantitative results are needed.
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Stimulation of the lateral hypothalamus (LH) produces antinociception that is modified by intrathecal alpha-adrenergic antagonists. Spinally-projecting noradrenergic neurons in the LH have not been identified, suggesting that the LH may innervate brainstem noradrenergic neurons, such as the A7 catecholamine cell group in the dorsolateral pontine tegmentum, that modify nociception at the level of the spinal cord dorsal horn. Recently we demonstrated in neuroanatomical studies that substance P-immunoreactive neurons in the LH project the A7 area. ⋯ In another set of experiments, the NK(1) receptor antagonist L-703-606 (5 microg) was microinjected near the A7 cell group following LH stimulation with carbachol. L-703-606 also abolished LH-induced antinociception. These results support the conclusion that antinociception produced by activating substance P neurons in the LH is mediated in part by the subsequent activation of spinally-projecting noradrenergic neurons in the A7 cell group.
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The effect of the nicotinic acetylcholine receptor (nAChR) agonists at the spinal level has not been well studied in neuropathic states. In the present report, we demonstrate the efficacy of intrathecal nicotinic agonists in partial sciatic nerve injury-induced neuropathy model mice. Intrathecal (i.t.) administration of (-)nicotine and (+)epibatidine, at doses without undesirable effects, had no antinociceptive action in sham-operated mice. ⋯ The GABA(A) antagonists bicuculline and picrotoxin significantly blocked the analgesic effects of muscimol as well as that of (-)nicotine and (+)epibatidine. On the other hand, i.t. injection of nicotinic antagonist mecamylamine and GABA(A) antagonist picrotoxin in sham-operated mice induced a thermal hyperalgesia without any effects in nerve-injured animals suggesting the presence of a tonic inhibitory tone on nociceptive transmission through the spinal cholinergic-GABAergic system. These results also suggest that the neuropathy-specific analgesic action of intrathecal nicotinic agonists was due to stimulation of this cholinergic-GABAergic system whose inhibitory tone had been reduced due to injury.
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Adenosine is an endogenous neuroprotectant via anti-excitotoxic effects at A(1) receptors, and blood flow promoting and anti-inflammatory effects at A(2a) receptors. Previous studies showed improved motor function after fluid percussion injury (FPI) in rats treated with the broad-spectrum adenosine receptor agonist 2-chloroadenosine (2-CA). We studied the effects of 2-CA, a specific A(1) agonist (2-chloro-N(6)-cyclopentyladenosine, CCPA), and a specific A(1) antagonist (8-cyclopentyl-1,3-dipropylxanthine, DPCPX) on motor task and Morris water maze (MWM) performance, and histopathology (contusion volume, hippocampal cell counts) after controlled cortical impact (CCI) in mice. ⋯ CA1 and CA3 counts were decreased in all groups versus sham. However, treatment with the selective A(1) agonist CCPA attenuated the CA3 cell loss (P<0.05 versus other treatment). We suggest that the beneficial effect of the broad spectrum adenosine receptor agonist 2-CA on motor function after CCI is not mediated solely by effects at the A(1) receptor.