Use of Botulinum Toxin for Limb Immobilization for Rehabilitation in Rats with Experimental Stroke.

Motor rehabilitation strategies after unilateral stroke suggest that the immobilization of the healthy, unimpaired limb can promote the functional recovery of a paretic limb. In rodents, this has been modeled using casts, harnesses, and other means of restricting the use of the non-paretic forelimb in models of experimental stroke. Here, we evaluated an alternative approach, using botulinum toxin injections to limit the function of the non-paretic forelimb.

A data-driven approach for evaluating multi-modal therapy in traumatic brain injury.

Combination therapies targeting multiple recovery mechanisms have the potential for additive or synergistic effects, but experimental design and analyses of multimodal therapeutic trials are challenging. To address this problem, we developed a data-driven approach to integrate and analyze raw source data from separate pre-clinical studies and evaluated interactions between four treatments following traumatic brain injury. Histologic and behavioral outcomes were measured in 202 rats treated with combinations of an anti-inflammatory agent (minocycline), a neurotrophic agent (LM11A-31), and physical therapy consisting of assisted exercise with or without botulinum toxin-induced limb constraint.

Food consumption and activity levels increase in rats following intranasal Hypocretin-1.

Hypocretin-1 (HC, orexin-A) is a neuropeptide involved in regulating physiological functions of sleep, appetite and arousal, and it has been shown that intranasal (IN) administration can target HC to the brain. Recent clinical studies have shown that IN HC has functional effects in human clinical trials. In this study, we use rats to determine whether IN HC has an immediate effect on food consumption and locomotor activity, whether distribution in the brain after IN delivery is dose-dependent, and whether MAPK and PDK1 are affected after IN delivery.

CCR2 deficiency impairs macrophage infiltration and improves cognitive function after traumatic brain injury.

Traumatic brain injury (TBI) provokes inflammatory responses, including a dramatic rise in brain macrophages in the area of injury. The pathway(s) responsible for macrophage infiltration of the traumatically injured brain and the effects of macrophages on functional outcomes are not well understood. C-C-chemokine receptor 2 (CCR2) is known for directing monocytes to inflamed tissues.

Beneficial effects of minocycline and botulinum toxin-induced constraint physical therapy following experimental traumatic brain injury.

Background: Effective recovery from functional impairments caused by traumatic brain injury (TBI) requires appropriate rehabilitation therapy. Multiple pathways are involved in secondary injury and recovery suggesting a role for multimodal approaches.

Objective: Here, we examined the efficacy of the anti-inflammatory agent minocycline and botulinum toxin (botox)-induced limb constraint with structured physical therapy, delivered alone or in combination, after a severe TBI produced by a controlled cortical impact in rats.

Post-injury conditioning with lipopolysaccharide or lipooligosaccharide reduces inflammation in the brain.

Background: Traumatic brain injury (TBI) is a leading cause of mortality and disability in the Western world. The first stage of TBI results from the mechanical damage from an impact or blast. A second stage occurs as an inflammatory response to the primary injury and presents an opportunity for clinical intervention.

Watermaze performance after middle cerebral artery occlusion in the rat: the role of sensorimotor versus memory impairments.

In rodent stroke models, investigation of deficits in spatial memory using the Morris watermaze may be confounded by coexisting sensory or motor impairments. To target memory specifically, we devised a watermaze protocol to minimize the impact of sensory and motor impairments in female Lister-hooded rats exposed to proximal electrocoagulation of the middle cerebral artery (MCAO). Rats were trained in a reference-memory task comprising 4 trials/day; trial 1 being a probe trial (platform absent for the first 60 seconds).

Microglial activation induced by brain trauma is suppressed by post-injury treatment with a PARP inhibitor.

Background: Traumatic brain injury (TBI) induces activation of microglia. Activated microglia can in turn increase secondary injury and impair recovery. This innate immune response requires hours to days to become fully manifest, thus providing a clinically relevant window of opportunity for therapeutic intervention.

Post-injury treatment with lipopolysaccharide or lipooligosaccharide protects rat neuronal and glial cell cultures.

Traumatic brain injury (TBI) is a major cause of disability in civilians and military personnel worldwide that is caused by the acceleration force of a primary shockwave, blast wind or the force of a direct contact. Following the primary injury, secondary injury is caused by activation of the immune response due to an influx of neuro-inflammatory cells, increased production of inflammatory cytokines, and edema. In ischemia models pre-conditioning with lipopolysaccharide (LPS) has been shown to be neuroprotective, and post-injury conditioning with LPS was found to be protective in a spinal cord and an acute brain injury model.

Detrimental effects of 17beta-oestradiol after permanent middle cerebral artery occlusion.

Oestrogen is a complex hormone whose role as a neuroprotectant in experimental stroke has been published in numerous studies. However, although some clinical studies report a reduction in stroke incidence by oestrogen replacement therapy in postmenopausal women, others have found increased mortality and morbidity after stroke. Diathermy occlusion of the proximal middle cerebral artery (MCAO), one of the most reproducible rodent stroke models, has consequently been employed to investigate physiologic and supraphysiologic doses of 17beta-oestradiol on ischaemic brain damage.

Differential effects of 17beta-estradiol upon stroke damage in stroke prone and normotensive rats.

We previously reported that during pro-estrus (high endogenous estrogen levels), brain damage after middle cerebral artery occlusion (MCAO) was reduced in stroke-prone spontaneously hypertensive rats (SHRSP) but not in normotensive Wistar Kyoto rat (WKY). In the present study, we examined the effect of exogenous estrogen on brain damage after MCAO in SHRSP and WKY. A 17beta-estradiol (0.

Essential role for verotoxin in sustained stress-activated protein kinase and nuclear factor kappa B signaling, stimulated by Escherichia coli O157:H7 in Vero cells.

The effects of Escherichia coli O157:H7 (strains E30480 and PM601) and the associated verotoxins (VTs), VT1 and VT2, on stress-activated protein kinase and nuclear factor kappa B (NF-kappaB) signaling were investigated with Vero cells, which are extremely sensitive to the cytotoxic effects of E. coli O157:H7 in vitro. Cell-free supernatants prepared from E30480 and PM601 cultures and purified VT1 and VT2 stimulated a strong and prolonged (>4-h) activation of both c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase.