Brain injury disrupts neuronal circuits, impacting neurological function. Selective and sensitive behavioral tests are required to explore neurological dysfunction, recovery and potential therapy. Previously we reported that the Whisker Nuisance Task (WNT), where whiskers are manually stimulated in an open field, shows sensory sensitivity in diffuse brain-injured rats. To further explore this somatosensory morbidity, we evaluated three additional whisker-dependent tasks: Gap Cross Test, a novel Angle Entrance Task and Whisker Guided Exploration Task. Brain-injured (n=11) and sham (n=8) rats were tested before midline fluid percussion brain injury (moderate: 2.0 atm) and one and four weeks after injury. For the WNT, we confirmed that brain-injured rats develop significant sensory sensitivity to whisker stimulation over 28 days. In the Gap Cross Test, where rats cross progressively larger elevated gaps, we found that animals were inconsistent in crossable distance regardless of injury. In the Angle Entrance Task, where rats enter 30°, 40°, 50° or 80° corners, rats performed consistently regardless of injury. In the Whisker Guided Exploration Task, where rats voluntarily explore an oval circuit, we identified significant decreases in the number of rears and reversals and changes in the predominant location (injured rats spend more time in the inside of the turn compared to the outside) after injury and increased thigmotaxis after sham and brain-injury. Both the WNT and Whisker Guided Exploration Task show injury-induced somatosensory behavioral morbidity; however, the WNT remains more sensitive in detecting brain injury, possibly due to imposed whisker stimulation that elicits agitation similar to the human condition.

Background Nitroglycerin (also known as glyceryl trinitrate (GTN)), a vasodilator best known for treatment of ischemic heart disease, has also been investigated for its potential therapeutic benefit in ischemic stroke. The completed Efficacy of Nitric Oxide in Stroke trial suggested that GTN has therapeutic benefit with acute (within 6 hours) transdermal systemic sustained release therapy. Objective To examine an alternative use of GTN as an acute therapy for ischemic stroke following successful recanalization. Methods We administered GTN IA following transient middle cerebral artery occlusion in mice. Because no standard dose of GTN is available following emergent large vessel occlusion, we performed a dose-response (3.12, 6.25, 12.5, and 25 .ig/.iL) analysis. Next, we looked at blood perfusion (flow) through the middle cerebral artery using laser Doppler flowmetry. Functional outcomes, including forced motor movement rotor rod, were assessed in the 3.12, 6.25, and 12.5 .ig/.iL groups. Histological analysis was performed using cresyl violet for infarct volume, and glial fibrillary activating protein (GFAP) and NeuN immunohistochemistry for astrocyte activation and mature neuron survival, respectively. Results Overall, we found that acute post-stroke IA GTN had little effect on vessel dilatation after 15 min. Functional analysis showed a significant difference between GTN (3.12 and 6.25 .ig/.iL) and control at post-stroke day 1. Histological measures showed a significant reduction in infarct volume and GFAP immunoreactivity and a significant increase in NeuN. Conclusions These results demonstrate that acute IA GTN is neuroprotective in experimental ischemic stroke and warrants further study as a potentially new stroke therapy. INTRODUCTIONStroke, disruption of blood flow to the brain due to vascular occlusion (ischemic) or bleeding (hemorrhagic), is the second leading cause of death worldwide and a leading cause of long-term disability. 1 Emergent large vessel occlusion (ELVO) is the most life-threatening and disabling type of ischemic stroke. Treatment options for ELVO consist of endovascular thrombectomy (ET) and/or IV tissue plasminogen activator (t-PA), but not all patients are eligible owing to exclusion criteria. [2][3][4] Furthermore, while ET and IV t-PA have improvedpatient survival, there is a need for adjunctive therapies to be used in tandem with or as a standalone treatment following successful vessel recanalization. 5 Any potential pharmacotherapy administration may be most successful and cause fewer systemic side effects if it is targeted at the site of ischemia. We hypothesize that improved treatment for ELVO might include rapid recanalization of the occluded vessel via ET combined with directed acute pharmacotherapy. To test such a targeted therapeutic approach, our laboratory uses an IA experimental model of pharmacotherapy administration in combination with transient tandem ipsilateral common carotid artery (CCA) and middle cerebral artery (MCA) occlusion, hereafter referred to as MCA ...

Early infection after stroke is associated with a poor outcome. We aimed to determine whether delayed infections (up to 76 days post-stroke) are associated with poor outcome at 90 days. Data came from the international Efficacy of Nitric Oxide Stroke (ENOS, ISRCTN99414122) trial. Post hoc data on infections were obtained from serious adverse events reports between 1 and 76 days following stroke in this large cohort of patients. Regression models accounting for baseline covariates were used to analyse fatalities and functional outcomes (modified Rankin Scale (mRS), Barthel Index, Euro-Qol-5D) at 90 days, in patients with infection compared to those without infection. Of 4011 patients, 242 (6.0%) developed one or more serious infections. Infections were associated with an increased risk of death (p < 0.001) and an increased likelihood of dependency (measured by mRS) compared to those of all other patients (p < 0.001). This remained when only surviving patients were analysed, indicating that the worsening of functional outcome is not due to mortality

Highlights Duration of joint inflammatory pain behaviour is prolonged in juvenile rats compared to adult rats. Spinal neuron hyperexcitability mirror pain behaviours of both juvenile and adult rats. Persistent upregulation of interleukin-6 uniquely observed in spinal cord of juvenile rats. Inhibition of spinal interleukin-6 activity rescued pain and normalised spinal neuron activity.