Normobaric hyperoxia retards the evolution of ischemic brain tissue toward infarction in a rat model of transient focal cerebral ischemia

Objectives: Oxygen therapy has been long considered a logical therapy for ischemic stroke. Our previous studies showed that normobaric hyperoxia (normobaric hyperoxia (NBO), 95% O₂ with 5% CO₂) treatment during ischemia reduced ischemic neuronal death and cerebromicrovascular injury in animal stroke models. In this study, we studied the effects of NBO on the evolution of ischemic brain tissue to infarction in a rat model of transient focal cerebral ischemia.

Methods: Male Sprague-Dawley rats were given NBO (95% O₂) or normoxia (21% O₂) during 90-min filament occlusion of the middle cerebral artery (MCAO), followed by 3 or 22.5 h of reperfusion. 2,3,5-triphenyltetrazolium chloride (TTC) staining was used to evaluate the longitudinal evolution of tissue infarction.

Results： In normoxic rats, MCA-supplied cortical and striatal tissue was infarcted after 90-min MCAO with 22.5 h of reperfusion. NBO-treated rats showed a 61.4% reduction in infarct size and tissue infarction mainly occurred in the ischemic striatum. When infarction was assessed at an earlier time point, i.e. at 3 h of reperfusion, normoxic rats showed significantly smaller but mature infarction (no TTC staining, white color), with the infarction mainly occurring in the striatum. Unexpectedly, NBO-treated rats only showed immature lesion (partially stained by TTC, light white color) in the ischemic striatum, indicating that NBO treatment also retarded the process of neuronal death in the ischemic core. Of note, NBO-preserved striatal tissue underwent infarction after prolonged reperfusion.

Conclusions： Our results demonstrate that NBO treatment given during cerebral ischemia retards the evolution of ischemic brain tissue toward infarction and NBO-preserved cortical tissue survives better than NBO-preserved striatal tissue during the phase of reperfusion.     

Erythropoietin reduces white matter damage in two-day-old rats exposed to hypoxic/ischemia injury

Objective: The aim of the study was to investigate whether erythropoietin (EPO) could protect against white matter damage (WMD) in a preterm equivalent neonatal rat hypoxic-ischemia (HI) model.

Methods: 113 two-day-old male rat pups were divided randomly into three groups: sham-treated, bilateral carotid artery occlusion (BCAO)-treated, BCAO + EPO-treated group. EPO (50 U/10 g body weight) or saline alone was administered intraperitoneally immediately after BCAO surgery. Body weight, brain weight, brain water content, and expression of myelin basic protein (MBP) were assessed at day 1, 3, 7, and 14 after HI insult. Morris water-maze (MWM) test was used to assess neurological behavior from day 31 to 35 after HI insult.

Results: Body weights of BCAO + EPO group were greater than those of BCAO group rats (P < 0.05). Specifically, at day 3 and 7 after HI, brain weights of BCAO + EPO-treated rats were higher than BCAO-treated animals (P < 0.05); at day 7 and 14 after HI, MBP of BCAO + EPO-treated rats were higher than BCAO-treated animals (P < 0.05). Similarly, the brain water content at day 3 after HI in BCAO + EPO-treated rats was lower than BCAO-treated animals (P < 0.05). The body weight, brain weight, brain water content, and MBP expression in BCAO + EPO-treated group were comparable to those in the sham-treated group. Spatial learning and memory of BCAO + EPO-treated rats was significantly improved over the BCAO-treated group and was comparable to the sham-operated animals.

Conclusion: EPO treatment could be a potential intervention in treating WMD for preterm infants.     

The mt-86 β aphasia battery: A subset of normative data in relation to age and level of school education

Abstract

The MT-86 β version of the Montréal-Toulouse Aphasia Battery has been devised for the clinical assessment of adult French speakers with language disorders. It includes 22 subtests for the appraisal of linguistic abilities in both encoding and decoding oral and written speech. The whole battery has been administered to a total of 143 neurologically healthy adults. This report deals with normative data for seven of the MT-86 β subtests, i.e. repetition, reading aloud, writing to dictation, copy, naming, verbal fluency, word and sentence picture-matching. These subtests correspond to classical tests used in aphasia batteries and are often discussed in the literature in relation to the effect of ageing of linguistic function. Mean scores, standard deviations and score ranges are reported and cut-off scores corresponding to the fifth percentile are suggested. Main effects of both age and education were found to exist in five subtests. Differences indicate better scores among younger versus older adults, and better scores among subjects with a higher versus a lower level of school education. Qualitative analyses of error types are also documented.     

Intracerebroventricular administration of ouabain alters synaptic plasticity and dopamine release in rat medial prefrontal cortex

Intracerebroventricular (ICV) administration of ouabain, a specific Na–K-ATPase inhibitor, in rats mimics the manic phenotypes of bipolar disorder and thus has been proposed as one of the best animal models of mania. Bipolar mania has been known to be associated with dysfunctions of medial prefrontal cortex (mPFC), a brain area critically involved in mental functions; however, the exact mechanism underlying these dysfunctions is not yet clear. The present study investigated synaptic transmission, synaptic plasticity, and dopamine release in Sprague-Dawley rat mPFC following ICV administration of ouabain (5 μl of 1 mM ouabain). The electrophysiological results demonstrated that ouabain depressed the short- and the long-term synaptic plasticity, represented by paired-pulse facilitation and long-term potentiation, respectively, in the mPFC. These ouabain-induced alterations in synaptic plasticity can be prevented by pre-treatment with lithium (intraperitoneal injection of 47.5 mg/kg lithium, twice a day, 7 days), which acts as an effective mood stabilizer in preventing mania. The electrochemical results demonstrated that ICV administration of ouabain enhanced dopamine release in the mPFC, which did not be affected by pre-treatment with lithium. These findings suggested that alterations in synaptic plasticity and dopamine release in the mPFC might underlie the dysfunctions of mPFC accompanied with ouabain administration-induced bipolar mania.     

Dopaminergic Function in the Psychosis Spectrum: An [18F]-DOPA Imaging Study in Healthy Individuals With Auditory Hallucinations

Background: The psychosis phenotype appears to exist in the population as a continuum, but it is not clear if subclinical psychotic symptoms and psychotic disorders share the same neurobiology. We investigated whether the dopaminergic dysfunction seen in psychotic disorders is also present in healthy, well-functioning people with hallucinations. Methods: We compared dopamine synthesis capacity (using 6-[¹⁸F]fluoro-L-DOPA [[¹⁸F]-DOPA] positron emission tomography imaging) in 16 healthy individuals with frequent persistent auditory verbal hallucinations (hallucinating group) with that in 16 matched controls. Results: There was no significant difference in dopamine synthesis capacity in the striatum, or its functional subdivisions, between groups and no relationship between subclinical psychotic symptom severity or schizotypal traits and dopamine synthesis capacity in the hallucinating group. Conclusions: Altered dopamine synthesis capacity is unlikely to underlie subclinical hallucinations, suggesting that although there may be a phenomenological psychosis continuum, there are distinctions at the neurobiological level.     

Impaired presynaptic function and elimination of synapses at premature stages during postnatal development of the cerebellum in the absence of CALEB (CSPG5/neuroglycan C)

Chicken acidic leucine‐rich EGF‐like domain‐containing brain protein (CALEB), also known as chondroitin sulfate proteoglycan (CSPG)5 or neuroglycan C, is a neural chondroitin sulfate‐containing and epidermal growth factor (EGF)‐domain‐containing transmembrane protein that is implicated in synaptic maturation. Here, we studied the role of CALEB within the developing cerebellum. Adult CALEB‐deficient mice displayed impaired motor coordination in Rota‐Rod experiments. Analysis of the neuronal connectivity of Purkinje cells by patch‐clamp recordings demonstrated impairments of presynaptic maturation of inhibitory synapses. GABAergic synapses on Purkinje cells revealed decreased evoked amplitudes, altered paired‐pulse facilitation and reduced depression after repetitive stimulation at early postnatal but not at mature stages. Furthermore, the elimination of supernumerary climbing fiber synapses on Purkinje cells was found to occur at earlier developmental stages in the absence of CALEB. For example, at postnatal day 8 in wild‐type mice, 54% of Purkinje cells had three or more climbing fiber synapses in contrast to mutants where this number was decreased to less than 25%. The basic properties of the climbing fiber Purkinje cell synapse remained unaffected. Using Sholl analysis of dye‐injected Purkinje cells we revealed that the branching pattern of the dendritic tree of Purkinje cells was not impaired in CALEB‐deficient mice. The alterations observed by patch‐clamp recordings correlated with a specific pattern and timing of expression of CALEB in Purkinje cells, i.e. it is dynamically regulated during development from a high chondroitin sulfate‐containing form to a non‐chondroitin sulfate‐containing form. Thus, our results demonstrated an involvement of CALEB in the presynaptic differentiation of cerebellar GABAergic synapses and revealed a new role for CALEB in synapse elimination in Purkinje cells.     

肝性脊髓病临床诊治分析

目的 分析肝性脊髓病的临床特点及治疗方法.方法 对临床确诊的6例肝性脊髓病的临床资料进行回顾性分析.结果 6例患者均表现为双下肢痉挛性瘫痪,虽经积极降氨等治疗,但恢复差.随访2例死于肝昏迷、消化道大出血,余2例2 a内未好转.结论 HM患者以下肢痉挛性瘫痪为主要表现,多为神经功能不可逆损害,内科治疗效果不佳,肝移植可能为目前最好的治疗方法.