Mild hypothermia facilitates the long-term survival of newborn cells in the dentate gyrus after traumatic brain injury by diminishing a pro-apoptotic microenvironment.

Although previous research has demonstrated that traumatic brain injury (TBI) accelerates the proliferation of neural stem cells in dentate gyrus of the hippocampus, most of these newborn cells undergo apoptosis in a traumatic microenvironment. Thus, promoting the long-term survival of newborn cells during neurogenesis is a compelling goal for the treatment of TBI. In this study, we investigated whether mild hypothermia (MHT) therapy, which mitigates the multiple secondary injury cascades of TBI, enhances the survival of newborn cells. SD rats were subjected to unilateral fluid percussion injury and received MHT therapy for 4h (33.5°C). Bromodeoxyuridine (BrdU) was administered to label the mitotic cells. Spatial learning and memory were evaluated with the Morris water maze test. Brain sections were immunostained with antibodies against BrdU, DCX (a neuroblast marker) or NeuN (a mature neuron marker). The apoptosis levels in the dentate gyrus were examined with antibodies against the apoptotic proteins FAS, FASL, Bcl-2 and cleaved caspase 3. The results indicated that MHT could significantly prevent TBI-induced cognitive impairments. At 1week after injury, the density of BrdU-immunoreactive cells significantly increased in both TBI and TBI+MHT rats. At 4weeks after injury, the density of BrdU-positive cells further increased in TBI+MHT rats, whereas the density declined in the TBI rats. The density of DCX-positive cells in SGZ of the hippocampus at 1week after injury in the TBI+MHT rats was significantly greater than in the TBI rats. Moreover, the density of NeuN-positive cells in the subgranular zone at 4weeks after injury and in the granule cell layer at 7weeks after injury was significantly increased in the TBI+MHT rats. The TBI+MHT rats displayed a lower level of apoptosis in the dentate gyrus compared with the TBI rats. These data indicate that TBI could only facilitate a burst of proliferation and short-term survival of newborn cells, whereas TBI+MHT could facilitate long-term survival and maturation of newborn cells through diminishing pro-apoptotic microenvironment. These results suggest that MHT-mediated neurogenesis may have an important therapeutic potential for the endogenous repair of TBI.

[Application of PiCCO monitoring in patients with neurogenic pulmonary edema].

OBJECTIVE: To evaluate the application of pulse induced contour cardiac output (PiCCO) monitoring in patients with neurogenic pulmonary edema (NPE), and to assess the accuracy of capacity parameters such as intra thoracic blood volume index (ITBVI) and global end diastolic volume index (GEDVI) and pressure parameters such as central venous pressure (CVP) in estimating severity of NPE, and to assess the prognostic significance of extravascular lung water index (EVLWI) on patients with NPE. METHODS: In this prospective study, 36 patients with NPE in the department of neurological intensive care unit (NICU) underwent PiCCO monitoring, including mean arterial pressure (MAP), cardiac index (CI), CVP, ITBVI, GEDVI, EVLWI, pulmonary vascular permeability index (PVPI). The correlation between ITBVI, GEDVI, CVP and EVLWI was assessed. According to the outcome, these patients were divided into nonsurvivor group and survivor group. The change in EVLWI before and after treatment was compared between two groups. RESULTS: ITBVI, GEDVI were significantly and positively correlated with EVLWI, for the former r =0.54, P<0.001, and for the latter r=0.62, P<0.0001, but there was no significant correlation between CVP and EVLWI, r= 0.12, P>0.05. PVPI, EVLWI were significantly and negatively correlated with oxygenation index (PaO2 / FiO2), for the former r=-0.55, P< 0.001, and for the latter r=-0.48, P<0.05. The difference in EVLWI level before treatment between survivor group and nonsurvivor group was not statistically significant (8.6±2.6 ml/kg vs. 9.4±1.8 ml/kg, P>0.05). In survivor group, EVLWI level obviously declined after treatment (6.92±1.64 ml/kg vs. 8.64±2.62 ml/kg, P<0.05), EVLWI level of survivor group was significantly lower than that of nonsurvivor group (6.92±1.64 ml/kg vs. 9.88±2.44 ml/kg, P<0.05). CONCLUSIONS: Capacity parameters such as GEDVI, ITBVI can assess EVLWI of NPE patients accurately and reliably. In NPE patients, the higher the PVPI and EVLWI, the lower the PaO2 / FiO2. By dynamic observation of the trends of EVLWI in NPE patients, we are able to assess the prognosis of these patients.

Ferulic acid potentiates pentobarbital-induced sleep via the serotonergic system.

Ferulic acid (4-hydroxy-3-methoxycinnamic acid, FA) is a widely distributed natural phenolic compound that is abundant in many plant tissues and foods. This study investigated possible mechanisms underlying the sedative-hypnotic effect of FA through behavioral pharmacology methods. FA showed dose-dependent sedative effects on locomotion activity in normal mice. FA also significantly potentiated pentobarbital-induced (45 mg/kg, i.p.) sleep by prolonging sleeping time and shortening sleep latency in a dose-dependent manner. These effects were augmented by the administration of 5-hydroxytryptophan (5-HTP), a precursor of 5-hydroxytryptamine (5-HT). With a sub-hypnotic dose of pentobarbital (25 mg/kg, i.p.), FA significantly increased the rate of sleep onset and exhibited a synergistic effect with 5-HTP (2.5 mg/kg, i.p.). Pretreatment with p-chlorophenylalanine (PCPA, an inhibitor of tryptophan hydroxylase) significantly decreased the duration of pentobarbital-induced sleep, whereas FA significantly reversed this effect. These results suggest that FA has sedative-hypnotic activity, possibly mediated by the serotonergic system.

[Clinical analysis of linezolid in treatment of infection with methicillin--resistant Staphylococcus in 14 neurosurgical patients].

OBJECTIVE: To evaluate the efficacy and safety of linezolid in the treatment of post-neurosurgical intracranial methicillin-resistant Staphylococcus (MRS) infection. METHODS: The data from 14 patients, admitted to neurological intensive care unit (ICU) of Medical College of Chinese People's Armed Police Forces between March 2009 and November 2011, were retrospectively analyzed. All these cases suffered from post-neurosurgical intracranial infection by MRS and received linezolid treatment. Blood and cerebrospinal fluid (CSF) were collected before and 7 days and 14 days after treatment for routine and bacteriological examinations to assess clinical efficacy and adverse reactions of linezolid. RESULTS: After 14-day treatment with linezolid, the clinical and laboratory parameters showed significant improvement: glucose (mmol/L) in CSF rose from 1.00 (0.65) to 3.15 (1.60), protein (mg/L) in CSF dropped from 2238.50 (2072.50) to 606.50 (217.30), white blood cell count [×106/L] in CSF fell from 920.00 (1587.50) to 30.00 (40.00), and the number of patients with CSF neutrophil ratio>0.20 was reduced from 14 to 1 (all P < 0.01). In addition, serum procalcitonin level (µg/L) was significantly reduced from 0.65 (1.16) to 0.08 (0.09) after linezolid therapy (P < 0.01). Total effective rate was 85.7% (12/14), and CSF bacterial clearance rate reached 100%. No adverse events were found during the treatment. CONCLUSION: Linezolid could effectively control post--neurosurgical intracranial MRS infection and alleviate the inflammatory responses with safety.

Stem cells modified by brain-derived neurotrophic factor to promote stem cells differentiation into neurons and enhance neuromotor function after brain injury.

OBJECTIVE: To promote stem cells differentiation into neurons and enhance neuromotor function after brain injury through brain-derived neurotrophic factor (BDNF) induction. METHODS: Recombinant adenovirus vector was applied to the transfection of BDNF into human-derived umbilical cord mesenchymal stem cells (UCMSCs). Enzyme linked immunosorbent assay (ELISA) was used to determine the secretion phase of BDNF. The brain injury model of athymic mice induced by hydraulic pressure percussion was established for transplantation of stem cells into the edge of injury site. Nerve function scores were obtained, and the expression level of transfected and non-transfected BDNF, proportion of neuron specific enolase (NSE) and glial fibrillary acidic protein (GFAP), and the number of apoptosis cells were compared respectively. RESULTS: The BDNF expression achieved its stabilization at a high level 72 hours after gene transfection. The mouse obtained a better score of nerve function, and the proportion of the NSE-positive cells increased significantly (P<0.05), but GFAP-positive cells decreased in BDNF-UCMSCs group compared with the other two groups (P<0.05). At the site of high expression of BDNF, the number of apoptosis cells decreased markedly. CONCLUSION: BDNF gene can promote the differentiation of the stem cells into neurons rather than glial cells, and enhance neuromotor function after brain injury.