Oxygen glucose deprivation inhibits the growth and ERK phosphorylation of neural progenitor cells in vitro

The neurogenic regions such as subventricular zone of the lateral ventricles could become ischemic in some clinical situations due to the blockage of blood vessels by blood clots. Hence the aim of this study is to investigate the effects of OGD on the growth of neural progenitor cells and the phosphorylation of ERK, which plays an important role in the growth of these cells. Oxygen glucose deprivation (OGD) for 4 h decreased the growth of neural progenitor cells in vitro and also decreased the phosphorylation of extracellular signal regulated kinase (ERK). Inhibition of the ERK pathway for 4 h using U0126 (10 μM) also decreased the growth of progenitor cells. These data suggest that a decline in the phospho-ERK content might decrease the growth of progenitor cells following OGD.     

Catechol-O-methyltransferase (COMT) inhibition reduces spinal nociceptive activity

Several variants of the catechol-O-methyltransferase (COMT) gene have recently been linked to pain sensitivity. In the present study, electrophysiological field potential recordings from the dorsal horn in rats were used to examine the spinal effect of reduced COMT activity. The data demonstrated that 30 mg/kg of the COMT inhibitor OR 486 reduced spinal nociceptive responses to painful stimuli (p ≤ 0.01, OR 486 vs. vehicle) and attenuated the expression of spinal long-term potentiation (LTP), an often studied model for central sensitization (p ≤ 0.01, HFS vs. HFS + OR 486). Our findings suggest that low COMT activity may have an antinociceptive effect in the spinal cord.     

Cholinergic modulation of intrinsic fibre-evoked excitatory transmission contains a nicotinic component in immature but not adult rat piriform cortex, in vitro

The piriform cortex (PC) is highly prone to epileptogenesis, particularly in immature animals, where decreased muscarinic modulation of PC intrinsic fibre excitatory neurotransmission is implicated as a likely cause. However, whether higher levels of acetylcholine (ACh) release occur in immature vs. adult PC remains unclear. We investigated this using in vitro extracellular electrophysiological recording techniques. Intrinsic fibre-evoked extracellular field potentials (EFPs) were recorded from layers II to III in PC brain slices prepared from immature (P14–18) and adult (P > 40) rats. Adult and immature PC EFPs were suppressed by eserine (1 μM) or neostigmine (1 μM) application, with a greater suppression in immature (∼40%) than adult (∼30%) slices. Subsequent application of atropine (1 μM) reversed EFP suppression, producing supranormal (∼12%) recovery in adult slices, suggesting that suppression was solely muscarinic ACh receptor-mediated and that some ‘basal’ cholinergic ‘tone’ was present. Conversely, atropine only partially reversed anticholinesterase effects in immature slices, suggesting the presence of additional non-muscarinic modulation. Accordingly, nicotine (50 μM) caused immature field suppression (∼30%) that was further enhanced by neostigmine, whereas it had no effect on adult EFPs. Unlike atropine, nicotinic antagonists, mecamylamine and methyllycaconitine, induced immature supranormal field recovery (∼20%) following anticholinesterase-induced suppression (with no effect on adult slices), confirming that basal cholinergic ‘tone’ was also present. We suggest that nicotinic inhibitory cholinergic modulation occurs in the immature rat PC intrinsic excitatory fibre system, possibly to complement the existing, weak muscarinic modulation, and could be another important developmentally regulated system governing immature PC susceptibility towards epileptogenesis.     

Baicalin prevents the production of hydrogen peroxide and oxidative stress induced by Aβ aggregation in SH-SY5Y cells

This study examined whether rats can simultaneously learn to associate lithium chloride (LiCl)-induced nausea with both contextual and intravascular taste cues. During the conditioning phase (4 days, 72 h apart), 32 male Long Evans rats were injected intraperitoneally with either isotonic saline (NaCl), lithium chloride (LiCl, 127 mg/kg), saline plus 2% saccharin (NaCl + Saccharin), or lithium chloride plus 2% saccharin (LiCl + Saccharin) immediately prior to a 30 min exposure to a novel context. 72 h following the final conditioning day, each animal was re-exposed to the context on a drug-free test day. The next day, animals received a 24 h 2-bottle preference test with a choice between water and a palatable saccharin solution. Results showed that animals treated with LiCl during conditioning, with or without saccharin, displayed significantly higher levels of conditioned gaping responses, indicative of nausea, upon re-exposure to the context, relative to NaCl and NaCl + Saccharin controls. Animals administered LiCl + Saccharin during conditioning also displayed significant conditioned taste avoidance to the saccharin solution during the two bottle choice test. These results indicate that systemic administration (intraperitoneal) of a LiCl + Saccharin solution is effective in simultaneously conditioning toxin elicited nausea to both internal (taste) and external (context) cues.     

Dorsal root ganglion neurons respond with prolonged extracellular signal-regulated protein kinase phosphorylation following noxious heat and cold stimulation

In the present study the time course of extracellular signal-regulated protein kinase phosphorylation (pERK1/2 appearance) in lumbar sensory dorsal root ganglia (DRG) was determined following a 5-min noxious heat or a noxious cold stimulus to the hind paw of the rat. The thermal stimuli were chosen to activate transient receptor potential (TRP) channels, but not to induce tissue damage. A quantitative analysis of phospho-ERK1/2 was performed by protein extraction and Western blot analysis. Western blot analysis showed that following the heat stimulus, phosphorylation of ERK1/2 increased 2–3-fold between 10 and 30 min in the DRG on the ipsilateral side. High levels were maintained from 30 min up to 16 h. Following the cold stimulus to the paw, pERK1/2 immediately increased 2-fold within 2 min in the DRG on the ipsilateral side, it declined within 2 h and reached a second peak at 4 h. In the DRGs on the contralateral side of the paw's heat or cold immersion the pERK1/2 remained low at all time points investigated. Fluorescence immunohistochemistry of the DRG following the thermal stimuli revealed an increased cytoplasmic staining for pERK1/2 in neurons. The present results show that following a 5-min nociceptive thermal stimulus sensory neurons respond with a characteristic long-lasting phosphorylation of ERK1/2.     

Behavioral and genetic effects promoted by sleep deprivation in rats submitted to pilocarpine-induced status epilepticus

The interaction between sleep deprivation and epilepsy has been well described in electrophysiological studies, but the mechanisms underlying this association remain unclear. The present study evaluated the effects of sleep deprivation on locomotor activity and genetic damage in the brains of rats treated with saline or pilocarpine-induced status epilepticus (SE). After 50 days of pilocarpine or saline treatment, both groups were assigned randomly to total sleep deprivation (TSD) for 6 h, paradoxical sleep deprivation (PSD) for 24 h, or be kept in their home cages. Locomotor activity was assessed with the open field test followed by resection of brain for quantification of genetic damage by the single cell gel electrophoresis (comet) assay. Status epilepticus induced significant hyperactivity in the open field test and caused genetic damage in the brain. Sleep deprivation procedures (TSD and PSD) did not affect locomotor activity in epileptic or healthy rats, but resulted in significant DNA damage in brain cells. Although PSD had this effect in both vehicle and epileptic groups, TSD caused DNA damage only in epileptic rats. In conclusion, our results revealed that, despite a lack of behavioral effects of sleep deprivation, TSD and PSD induced genetic damage in rats submitted to pilocarpine-induced SE.     

Matrix metalloproteinase-9 (MMP-9) expression and extracellular signal-regulated kinase 1 and 2 (ERK1/2) activation in exercise-reduced neuronal apoptosis after stroke

Exercise preconditioning has been shown to reduce neuronal damage in ischemic/reperfusion (I/R) injury. ERK1/2 signaling in injury has been thought to modulate neuroprotection. In this study, we investigated the effects of ERK1/2 activation on the expression and activity of MMP-9 and downstream neuronal apoptosis. Adult male Sprague–Dawley rats were subjected to 30 min of exercise on a treadmill for 3 weeks. Stroke was induced by a 2-h middle cerebral artery (MCA) occlusion using an intraluminal filament. Apoptotic protein caspase-3 and neuronal apoptosis in cortex and striatum was determined by Western blot at 24 h reperfusion and TUNEL staining at 48 h reperfusion in 5 I/R injury groups: no treatment, MMP-9 inhibitor (doxycycline), pre-ischemic exercise, exercised animals undergone ERK1/2 inhibition (U0126), and dual inhibition of ERK1/2 and MMP-9 in exercised ischemic rats. Cerebral MMP-9 expression in ischemic rats with different treatment was determined at 6, 12 and 24 h reperfusion by real-time PCR for mRNA, Western blot for protein and zymography for enzyme activity. Exercise preconditioning significantly (p < 0.05) reduced apoptosis determined by caspase-3 and TUNEL. In non-exercised rats, doxycycline treatment had significant (p < 0.05) reductions in apoptosis after I/R injury. The dual ERK1/2–MMP-9 inhibited exercised animals had significantly (p < 0.05) reduced neuronal apoptosis that was similar to that seen in exercised ischemic rats. MMP-9 expression in I/R injury was significantly (p < 0.05) reduced in the exercised animals as compared to non-exercised controls. When ERK1/2 was inhibited, the reduced MMP-9 expression was reversed to the level seen in the non-exercised controls. This study has suggested that exercise-induced neuroprotection in I/R injury may be mediated by MMP-9 and ERK1/2 expression, leading to a reduction in neuronal apoptosis.     

Protective effect of albumin on VEGF and brain edema in acute ischemia in rats

Vascular endothelial growth factor (VEGF) is known to be an important stroke-related pathogenic factor for the formation of brain edema. We examined the therapeutic effect of human serum albumin on VEGF expression in acute ischemic stroke. Adult male Sprague–Dawley (SD) rats were subjected to Middle Cerebral Artery Occlusion (MCAO), the suture was withdrawn 2 h later, and 25% albumin (1.25 g/kg) or saline (5 ml/kg) was administered intravenously after reperfusion. The model was evaluated by 2,3,5-triphenyl-tetrazolium chloride (TTC) staining, neurological deficits and brain water content. Serum albumin level was determined. VEGF expression was studied by enzyme linked immunosorbent assay (ELISA), quantitative real-time PCR and immunohistochemistry. We demonstrated that albumin administration maintained the serum albumin at a higher level than the sham group at 6 h, 1 d, 2 d and 3 d after MCAO, and significantly improved the neurological deficits and decreased the brain water content. In addition, the strong up-regulation of VEGF expression at 6 h and 1 d after MCAO can be attenuated by albumin administration. However, albumin administration had no significant depressing effect on VEGF expression at 2 d, 3 d and 5 d after MCAO in the cortex and hippocampus. Strong up-regulation of VEGF immunoreactivity was noted in the saline group in the blood–brain barrier (BBB), and in neurons surrounding the peri-infarct area and periventricular area at 24 h after MCAO. The expression of VEGF in the albumin group was much weaker. Furthermore, there were high correlations between the brain water content with the serum albumin level, with serum VEGF protein level, and with brain VEGF mRNA expression at 24 h after MCAO. In conclusion, maintaining the serum albumin at a higher level, and attenuating endogenous VEGF expression at 6 h and 1 d, but not 2 d, 3 d, or 5 d after MCAO, may partially contribute to the protective effects of albumin on reduction of brain edema in the early stage of ischemia.     

Grp78表达对人肝细胞癌细胞外信号调节激酶1/2活性和表达的影响

目的 通过检测葡萄糖调节蛋白78(Grp78)、细胞外信号调节激酶(ERK1/2)、磷酸化ERK1/2在肝细胞癌手术切除组织中的表达,并在SMMC-7721细胞中干预Grp78的表达,探讨Grp78对ERK1/2激酶的调控作用。 方法 应用免疫组织化学方法（IHC）和免疫印迹法检测47例肝细胞癌手术切除组织样本中Grp78,ERK1/2的表达和ERK1/2磷酸化水平;在高表达Grp78的肝细胞癌细胞系SMMC-7721中,通过用小RNA干扰Grp78的表达来探讨Grp78表达水平,改变对ERK1/2活性及表达的影响。 结果 在肝细胞癌组织样本中,Grp78的表达情况与ERK1/2和磷酸化ERK1/2的表达明显呈正相关。在SMMC-7721细胞中Grp78高表达促进ERK1/2的磷酸化,应用RNA干扰特异性下调Grp78高表达细胞中Grp78水平可以抑制ERK1/2的磷酸化。 结论 Grp78参与调解ERK1/2信号通路,并且在肝细胞癌临床治疗方面可能成为潜在的治疗靶点。     

The lateral habenula regulates defensive behaviors through changes in 5-HT-mediated neurotransmission in the dorsal periaqueductal gray matter

Chemical stimulation of the lateral nucleus of the habenula (LHb), an area implicated in the regulation of serotonergic activity in raphe nuclei, affects the acquisition of inhibitory avoidance and escape expression of rats submitted to the elevated T-maze test of anxiety. Here, we investigated whether facilitation of 5-HT-mediated neurotransmission in the dorsal periaqueductal gray (dPAG) accounts for the behavioral consequences in the elevated T-maze induced by chemical stimulation of the LHb. The dPAG in the midbrain, which is innervated by 5-HT fibers originating from the dorsal raphe nucleus (DRN), has been consistently implicated in the genesis/regulation of anxiety- and fear-related defensive responses. The results showed that intra-dPAG injection of WAY-100635 or ketanserin, 5-HT_1A and 5-HT_2A/2C receptor antagonists, respectively, counteracted the anti-escape effect caused by bilateral intra-LHb injection of kainic acid (60 pmol/0.2 μl). Ketanserin, but not WAY-100635, blocked kainic acid's facilitatory effect on inhibitory avoidance acquisition. Overall, the results suggest that the pathway connecting the LHb to the DRN is involved in the control of 5-HT release in the dPAG, and facilitation of 5-HT-mediated neurotransmission in the latter area distinctively impacts upon the expression of anxiety- and fear-related defensive behaviors. While stimulation of 5-HT_1A receptors selectively affects escape performance, 5-HT_2A/2C receptors modulate both inhibitory avoidance and escape.     

Neuroprotective effects of Epigallocatechin-3-gallate (EGCG) in optic nerve crush model in rats

Epigallocatechin-3-gallate (EGCG), the major catechin found in green tea, is a powerful antioxidant and has anti-inflammatory with neuroprotective potential. This study aims to investigate the neuroprotective effects of EGCG in an optic nerve crush (ONC) model in rats. Seventy-two Wistar rats were randomly divided into four groups: normal control (group A), sham operation + EGCG (group B), ONC + vehicle (group C), and ONC + EGCG (group D). The rats were treated intraperitoneally and orally with either vehicle or EGCG (25 mg/kg, injected daily for 5 days and 2 mg/kg orally daily afterwards). Two days after the first injection, an ONC injury was performed by using a micro optic nerve clipper with 40 g power at approximately 2 mm from the optic nerve head for 60 s. Fluorogold was injected into the bilateral superior colliculi 5 days before sacrifice and fluorescent gold-labelled retinal ganglion cells (RGCs) were counted under fluorescence microscopy on days 7, 14 and 28 after ONC. The expression of Neurofilament triplet L (NF-L) was measured via immunohistochemical and Western blotting analysis. In group C, a progressive loss of RGCs was observed after ONC. In contrast, the density of RGCs was significantly higher in group D (p = 0.009, independent samples t-test) on day 7 after ONC, and statistical differences were obtained on days 14 and 28 (p = 0.026 and p = 0.019, respectively, independent samples t-test). The results of immunohistochemical and Western blotting analysis showed significantly higher NF-L protein expression in group D in comparison with group C on days 7, 14 and 28 after ONC. These findings suggest that there are protective effects of EGCG on RGCs after ONC, indicating EGCG might be a potential therapeutic agent for optic nerve diseases.     

Rapid and highly resolving associative affective learning: Convergent electro- and magnetoencephalographic evidence from vision and audition

Various pathway models for emotional processing suggest early prefrontal contributions to affective stimulus evaluation. Yet, electrophysiological evidence for such rapid modulations is still sparse. In a series of four MEG/EEG studies which investigated associative learning in vision and audition using a novel MultiCS Conditioning paradigm, many different neutral stimuli (faces, tones) were paired with aversive and appetitive events in only two to three learning instances. Electrophysiological correlates of neural activity revealed highly significant amplified processing for conditioned stimuli within distributed prefrontal and sensory cortical networks. In both, vision and audition, affect-specific responses occurred in two successive waves of rapid (vision: 50–80 ms, audition: 25–65 ms) and mid-latency (vision: >130 ms, audition: >100 ms) processing. Interestingly, behavioral measures indicated that MultiCS Conditioning successfully prevented contingency awareness. We conclude that affective processing rapidly recruits highly elaborate and widely distributed networks with substantial capacity for fast learning and excellent resolving power.     

Cytomegalovirus-induced salivary gland pathology: AREG,FGF8, TNF-α, and IL-6 signal dysregulation and neoplasia

Mucoepidermoid carcinoma (MEC) is the most common malignant tumor originating in major and minor salivary glands (SGs). Although the precise multifactorial etiology of human SG-MEC is largely unknown, we have recently shown that cytomegalovirus (CMV) is an important component of MEC tumorigenesis. Despite the well-documented overexpression of the EGFR → ERK signaling pathway in SG-MEC, there has been limited to no clinical success with inhibition of this pathway. Using our previously characterized mouse model of CMV-induced SG dysplasia/neoplasia, we report that inhibitors of the EGFR → ERK pathway do not ameliorate or rescue well-established pathology, either singly or in combination, but they do inhibit the evolution of progressive pathogenesis (“disease tolerance”) in the face of mounting CMV burden. Failure to rescue SG pathology, suggested a possible increase in the ligand levels of alternative pathways that share cell proliferation and survival effectors (e.g. ERK and PI3K). Here we present evidence of a highly significant upregulation of ligands for the EGFR, FGFR, IL-6R, and TNFR signaling pathways, all of which converge upon the Raf/MEK/ERK amplifier module. This explains our finding that even in the presence of the highest nontoxic dose of an ERK phosphorylation inhibitor, pERK is undiminished. Given the considerable pathway crosstalk, a deep understanding of subversion and dysregulation of the SG interactome by CMV is a priori quite daunting. Circumventing this dilemma, we present evidence that concurrent inhibition of ERK phosphorylation (U0126) and CMV replication (acyclovir) obviates progressive pathogenesis and results in complete SG rescue (tumor regression). These findings provide a mechanistic foundation for potential clinical trials that utilize similar concurrent treatment with extant FDA-approved drugs.     

Expression of the P/Q (Cav2.1) calcium channel in nodose sensory neurons and arterial baroreceptors

It was previously found that persistent inflammatory pain state resulted in enhancement of synaptic connections and efficacy in direct entorhinal-hippocampal (EC-HIP) pathways. In the current study, the roles of two subtypes of group I metabotropic glutamate receptors in the above processes were evaluated. Similarly, pain-related spatial and temporal synaptic enhancement model was stably achieved by the multi-electrode array (8 × 8) recordings in the hippocampal slices of rats pre-treated with intraplantar (i.pl.) bee venom (BV) injection. I.pl. saline injection was used as control. Inhibition of mGluR1 by a selective antagonist 7-hydroxyiminocyclopropan [b] chromen-1α-carboxylic acid ethyl ester (CPCCOEt) resulted in a dramatic increase in synaptic connections in the hippocampal slices of rats treated by BV, but not by saline. However, inhibition of mGluR5 by a selective antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) produced no spatial change from either of the two groups. Temporally, the BV-enhanced LTP could be further incremented by antagonism of mGluR1 with CPCCOEt perfusion when plateau LTP was well established. However, the BV-enhanced LTP was significantly suppressed by antagonism of mGluR5 with MPEP. Neither of the two drugs affected magnitude of LTP in rats treated by i.pl. saline. Taken together with our previous results, it is suggested that mGluR1 be involved in tonic inhibition of EC-HIP synaptic enhancement, while mGluR5 be involved in maintenance of persistent inflammatory pain-associated EC-HIP synaptic enhancement that is largely based upon activation of ionic glutamate receptors.     

Effect of nitric oxide synthase inhibitor and NMDA receptor antagonist on the development of nicotine sensitization of nucleus accumbens dopamine release: An in vivo microdialysis study

We have previously found that the neuronal nitric oxide synthase inhibitor N-nitro-l-arginine (l-NNA) and the noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist MK-801 prevent behavioral sensitization to nicotine. This study aimed to investigate the effect of l-NNA and MK-801 on a neurochemical component of nicotine sensitization by evaluating the effect of the drugs on nicotine sensitization of nucleus accumbens dopamine (DA) release. Sprague–Dawley rats were pretreated with l-NNA (15 mg/kg, i.p.), MK-801 (0.3 mg/kg, i.p.), or saline 30 min before injection of nicotine (0.4 mg/kg, s.c., once daily) for seven consecutive days. Twenty-four hours after the last drug injection, animals were challenged with local perfusion of 5 mM nicotine into the shell of nucleus accumbens for 60 min and DA release was monitored using in vivo microdialysis. In rats treated with repeated nicotine, acute nicotine challenge induced a greater increase of accumbal DA release than in saline-treated animals (maximal DA response = 969 ± 235% (mean ± S.E.M.) of basal level versus 520 ± 93%, p = 0.042). Co-administration of l-NNA or MK-801 with nicotine attenuated an increase of DA release elicited by acute nicotine challenge, compared with nicotine alone (maximal DA response = 293 ± 58% and 445 ± 90% of basal level, respectively versus 969 ± 235%, p = 0.004 and p = 0.013, respectively). These data demonstrate that l-NNA and MK-801 block the development of nicotine sensitization of nucleus accumbens DA release, further supporting the involvement of nitric oxide and NMDA receptors in the development of behavioral sensitization to nicotine.     

Long-term normalization of blood pressure in SHR and 1-kidney 1-clip rats by synthetic precursor of stable PAF analogue without systemic effects in normotensive rats

This study characterized the actions of the newly synthesized PAF precursor 1-hexadecyl-2-alkylcarbamoyl-glycerol (HAG) on blood pressure (BP) in male spontaneously hypertensive rats (SHR), SHR-stroke prone (SHRSP) and Wistar rats with 1-kidney 1-clip (1K1C) renovascular hypertension used as experimental models of human primary and secondary hypertension. Systolic blood pressure (SBP) in the tail artery and mean arterial pressure (MAP) in the abdominal aorta were measured by tail plethysmography and invasive pressure transducer, respectively. Intravenous treatment with 1 mg/kg HAG in SHR resulted in a rapid decline of MAP from 151 ± 4 to 127 ± 4 mm Hg in 50 min (p < 0.001) that was maintained for 24 h after injection (128 ± 5 mm Hg, p < 0.01). We also observed a profound hypotensive effect of HAG in SHRSP but not in normotensive Wistar rats. In 1K1C rats, the magnitude of the BP decline evoked by HAG was correlated with MAP measured before drug administration (R = 0.74, p < 0.005). In 1K1C rats with SBP > 140 mm Hg, 5 mg/kg/48 h HAG, given orally for 14 days, decreased SBP by 20-30 mm Hg without an increase in the death rate and other adverse effects. Thus, our results show that intravenous and oral administration of HAG led to a long-lasting reduction of BP in experimental models of primary and secondary hypertension. In contrast to PAF and its derivatives, the hypotensive action of HAG was preserved for 24 h after a single administration, was absent in normotensive animals, and was not accompanied by visible side-effects, at least during 2 weeks of treatment.     

Choline acetyltransferase expression in rat prefrontal cortex and hippocampus after acute and chronic exposure to amisulpride,haloperidol, and risperidone

Recently, there has been an increasing concern that atypical antipsychotics as well as typical ones may cause detrimental effects on cognitive function. Supporting evidence comes from many preclinical studies demonstrating that long-term administration of haloperidol, risperidone, and ziprasidone reduced choline acetyltransferase (ChAT) expression in rat hippocampus (HIP). However, to the best of our knowledge, no studies have examined the effects of amisulpride on ChAT expression in rats. Therefore, the aim of this study was to investigate the effects of acute and chronic administration of amisulpride, haloperidol, and risperidone on ChAT expression in the rat prefrontal cortex (PFC) and HIP. Animals received daily intraperitoneal (i.p.) injections of amisulpride (5 or 100 mg/kg), haloperidol (1 or 2 mg/kg), risperidone (1 or 2 mg/kg) or vehicle for 7 or 45 days. One day after the last injection, rats were sacrificed. ChAT immunoreactivity was assessed with immunofluorescence staining. Target areas of brain were PFC and HIP (CA1, CA3 and DG). The short-term administration of haloperidol and risperidone produced significant decrease of ChAT immunoreactivity in the PFC and HIP compared to vehicle whereas amisulpride had no effects on ChAT immunoreactivity in the PFC and HIP. In long-term study, haloperidol and risperidone decreased ChAT-positive cells and/or fiber pixel density in the PFC and HIP whereas amisulpride decreased ChAT-positive cells in the PFC and had no effects on fiber pixel density of ChAT in the HIP. The results suggest that both short-term and long-term administration of haloperidol and risperidone, and long-term administration of amisulpride may produce detrimental effects on cognitive function by reducing ChAT expression in the PFC and/or HIP.     

Atorvastatin prevents early apoptosis after thoracic spinal cord contusion injury and promotes locomotion recovery

The systemic administration of atorvastatin has been shown to be neuroprotective after spinal cord injury (SCI), by decreasing the inflammatory response at the lesion site and by reducing neuronal and oligodendrocyte apoptosis. The latter effect spares white matter at the injury site and improves locomotion. The aim of this study was to confirm the neuroprotective efficacy of atorvastatin as well as its early action in limiting apoptosis with its administration post-SCI. Female Sprague-Dawley rats received an intra peritoneal injection of: (1) statin/saline (5 mg/kg) at 2 h after the contusion injury; (2) physiological saline at 2 h post-SCI; or (3) physiological saline without injury. Statin-treated rats showed significant (p < 0.05) improvement in locomotion at week 4 post-SCI compared to vehicle-treated animals. Explaining this outcome, caspase-3 activity decreased by 50% (p < 0.05), and the histological TUNEL method revealed a decrease of approximately 20% in apoptotic cells at the injury site (p < 0.01) at 4 h post-SCI in atorvastatin-treated rats in comparison to vehicle-treated controls. These data demonstrate that atorvastatin is effective after experimental spinal cord contusion injury in preventing early apoptosis at the injury site within 2 h post-administration.