Ulriksenhanson1029
Background Despite multiple experimental models of traumatic brain injury (TBI) being available, objective assessment of gait and motor function in rodents remains difficult; therefore, we studied the value of the CatWalk XT® gait analysis as an observer independent, automated method for outcome assessment in one of the most frequently used preclinical TBI model, the controlled cortical impact (CCI), in mice. Methods C57Bl/6 mice were subjected to either right parietal CCI or a sham procedure. Functional outcome was assessed using the CatWalk XT® (Version 10.6) as well as the hole board test at days one, three and seven after trauma induction. Results CCI led to diffuse, asymmetric and bilateral disturbances of both static and dynamic parameters in the CatWalk XT® gait analysis. The CatWalk XT® detected even minimal but statistically significant impairments that could not have been detected by clinical assessments. Impairments of static parameters were most pronounced within the first three days and diminished thereafter, while dynamic parameters were impaired until seven days after CCI. Fittingly, mice explored the hole board significantly less on day three trauma induction. Conclusions The CatWalk XT® is a valid tool for objective assessment of motor function in the acute phase after controlled cortical impact TBI in mice. Similar to observations made in humans, CCI leads to impairments of both static and dynamic parameters of gait and motor function which persist throughout the first week after the injury.The influence of parental support on child pain experiences is well recognised. Accordingly, animal studies have revealed both short- and long-term effects of early life stress on nociceptive responding and neural substrates such as endocannabinoids. The endocannabinoid system plays an important role in mediating and modulating stress, social interaction, and nociception. This study examined the effects of maternal support or acute isolation on nociceptive responding of female rats to a range of stimuli during the juvenile pre-adolescent period and accompanying changes in the endocannabinoid system. The data revealed that juvenile female Sprague Dawley rats (PND21-24) isolated from the dam for 1 h prior to nociceptive testing exhibited increased latency to withdraw in the hot plate test and increased mechanical withdrawal threshold in the Von Frey test, compared to rats tested in the presence of the dam. Furthermore, isolated rats exhibited reduced latency to respond in the acetone drop test and enhanced nociceptive responding in the formalin test when compared to dam-paired counterparts. Anandamide, but not 2-AG, levels were reduced in the prefrontal cortex of dam-paired, but not isolated, juvenile rats following nociceptive testing. There was no change in the expression of CB1, FAAH or MAGL; however, CB2 receptor expression was reduced in both dam-paired and isolated rats following nociceptive testing. Taken together the data demonstrate that brief social isolation or the presence of the dam modulates nociceptive responding of juvenile rat pups in a modality specific manner, and suggest a possible role for the endocannabinoid system in the prefrontal cortex in sociobehavioural pain responses during early life.Purpose To explore the effect of vagal nerve stimulation (VNS) on spontaneous brain activity in patients with drug-resistant epilepsy (DRE). Methods 15 patients and eight healthy controls (HC) were enrolled and scanned by resting-state functional MRI to investigate changes in the fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo). A two-sample t-test or paired sample t-test was used to compare activity between the HCs, preoperative patients (EP-pre), and postoperative patients (EP-post). We also performed correlation analyses to examine the seizure improvement ratio. Results The voxel-level analyses indicated that, compared with the HC, the EP-pre group exhibited decreased or increased fALFF and ReHo in the frontal cortex, temporal cortex, precentral/postcentral gyrus, amygdala, insula, cerebellum, and lingual gyrus. TPAactivator Furthermore, compared with the EP-pre group, the EP-post group exhibited decreased or increased fALFF and ReHo in the frontal cortex, temporal cortex, precentral gyrus, insula, anterior/median cingulate gyri, and cerebellum. The regions of interest-level analyses indicated that, compared with HC, the EP-pre group exhibited decreased fALFF or ReHo in the caudate nucleus, supramarginal gyrus, precuneus and middle temporal gyrus. Furthermore, compared with the EP-pre group, the EP-post group exhibited increased fALFF or ReHo in the olfactory cortex, gyrus rectus, and superior temporal gyrus. Increased ReHo in the right superior or middle temporal gyrus was positively correlated with the improvement ratio. Conclusions Altered regional activity in DRE patients was reorganized after 3 months of stimulation. Increased ReHo in the right superior or middle temporal gyrus was implicated in VNS-induced improvement in seizure frequency.Apart from its well-established therapeutic activity on bipolar disorder and depression, lithium exerts neuroprotective activity upon neurodegenerative disorders, such as traumatic brain injury (TBI). However, the cellular signaling mechanisms mediating lithium's neuroprotective activity and long-term dose- and time-dependent effects on close and remote proximity are largely unknown. Herein, we tested prophylactic and acute effects of lithium (2 mmol/kg) after cold- induced TBI. In both conditions, treatments with lithium resulted in reduced infarct volume and apoptosis. Its acute treatment resulted in the increase of Akt, ERK-1/2 and GSK-3 α/β phosphoylations. Interestingly, its prophylactic treatment instead resulted in decreased phosphorylations of Akt, ERK-1/2, p38, JNK-1 moderately and GSK-3 α/β significantly. Then, we tested subacute (35-day follow-up) role of low (0.2 mmol/kg) and high dose (2 mmol/kg) lithium and revealed that high dose lithium group was the most mobile so the least depressed in the tail suspension test. Anxiety level was assessed by light-dark test, all groups' anxiety levels were decreased with time, but lithium had no effect on anxiety like behavior. When subacute effects of injury and drug treatment were evaluated on the defined brain regions, infarct volume was decreased in the high dose lithium group significantly. In contrast to other brain regions, hippocampal atrophies were observed in both lithium treatment groups, which were significant in the low dose lithium group in both hemispheres, which was associated with the reduced cell proliferation and neurogenesis. Our data demonstrate that lithium treatment protects neurons from TBI. However, long term particularly low-dose lithium causes hippocampal atrophy and decreased neurogenesis.