Brain research
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Comparative Study
Acetylcholine and choline dynamics provide early and late markers of traumatic brain injury.
We assessed acetylcholine (ACh) and choline (Ch) dynamics 2.5 h, 1, 4 and 14 days after cerebral cortex impact injury or craniotomy only in adult male Sprague-Dawley rats. Cortical endogenous ACh (D0ACh), endogenous free Ch (D0Ch), deuterium-labeled Ch (D4Ch), and ACh synthesized from D4Ch (D4ACh) were measured by gas-chromatography mass-spectrometry after intravenous injection of D4Ch followed in 1 min by microwave fixation of the brain. D0Ch increased in and around the impact up to 700% of control within 1 day after trauma. ⋯ In conclusion, D0Ch tissue level was an early marker of trauma, while 14 days after trauma Ch uptake from blood was enhanced in and around the traumatized cortex. Craniotomy by itself induced a generalized increase in ACh turnover 1 day after this minimal trauma. Choline acetyltransferase activity was reduced in the impact center region but not affected in the adjacent and contralateral regions or by craniotomy.
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Spinal gamma-aminobutyric acid (GABA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors have been implicated in the mechanisms of neuropathic pain after nerve injury; however, how these two receptors interact at the spinal level remains unclear. Here we show that intrathecal midazolam through activation of spinal GABAA receptors attenuated the expression and function of spinal AMPA receptors in rats following peripheral nerve injury. ⋯ The inhibitory effects of midazolam (10, 20 mug) on neuropathic pain behaviors and AMPA receptor expression were prevented by co-administration of midazolam with the GABAA receptor antagonist bicuculline (3 mug), whereas intrathecal treatment with bicuculline (1 or 3 mug) alone in naive rats induced the upregulation of spinal AMPA receptor expression and nociceptive responses, indicating a tonic regulatory effect from endogenous GABAergic activity on the AMPA receptor expression and spinal nociceptive processing. These results indicate that modulation of spinal AMPA receptor expression and function by the GABAergic activity may serve as a mechanism contributory to the spinal nociceptive processing.
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Curcuma longa is a major constituent of the traditional Chinese medicine Xiaoyao-san, which has been used to effectively manage stress and depression-related disorders in China. Curcumin is the active component of curcuma longa, and its antidepressant effects were described in our prior studies in mouse models of behavioral despair. We hypothesized that curcumin may also alleviate stress-induced depressive-like behaviors and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. ⋯ In addition, we also found that the chronic stress procedure induced a down-regulation of brain-derived neurotrophic factor (BDNF) protein levels and reduced the ratio of phosphorylated cAMP response element-binding protein (pCREB) to CREB levels (pCREB/CREB) in the hippocampus and frontal cortex of stressed rats. Furthermore, these stress-induced decreases in BDNF and pCREB/CREB were also blocked by chronic curcumin administration (5 or 10 mg/kg, p.o.). These results provide compelling evidence that the behavioral effects of curcumin in chronically stressed animals, and by extension humans, may be related to their modulating effects on the HPA axis and neurotrophin factor expressions.
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Inflammation is an important factor for hypoxia-ischemia (HI) brain injury. Interleukin (IL)-18 is a proinflammatory cytokine which may be a contributor to injury in the immature brain after HI. To investigate the effects of post-HI hypothermia on IL-18 in the developing brain, 7-day-old rats were subjected to left carotid artery ligation followed by 8% oxygen for 60 min and divided into a hypothermia group (rectal temperature 32 degrees C for 24 h) and a normothermia group (36 degrees C for 24 h). ⋯ The number of ameboid microglia (AM) in the normothermia group was significantly increased in cortex and CC, compared with the number in controls, but there were very few ramified microglia (RM) in these areas. In contrast, the number of AM in the hypothermia group was significantly decreased in cortex and CC, compared with the number in the normothermia group, and there were no significant differences in the number of AM and RM between the hypothermia group and controls. In conclusion, we found that IL-18 mRNA and the protein level were attenuated by post-HI hypothermia and that post-HI hypothermia may decrease microglia activation in the developing brain.
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Laser Speckle Contrast Analysis (LASCA), a novel, high-resolution blood flow imaging method, was performed on rat somatosensory cortex during functional activation. In the same animals, cerebral blood flow (CBF) was measured with Laser Doppler Flowmetry. To obtain a quantitative estimate of the underlying neuronal activity, somatosensory evoked potentials were recorded simultaneously with an epidural EEG. ⋯ LASCA imaging localizes the highest relative changes of CBF in microcirculatory areas, with a smaller contribution by larger vessels. This study demonstrates that LASCA is a reliable method that provides 2D-imaging of CBF changes that are comparable to LDF measurements. It further suggests that functional neuroimaging methods based on CBF enhance areas of microcirculation and thus might prove more accurate in localizing neural activity than oxygenation related methods like BOLD-fMRI.