Voluntary forced use of the impaired limb following stroke facilitates functional recovery in the rat.

Constraint induced movement therapy (CIMT), which forces use of the impaired arm following stroke, improves functional recovery. The mechanisms underlying recovery are not well understood, necessitating further investigation into how rehabilitation may affect neuroplasticity using animal models. Animal motivation and stress make modelling CIMT in animals challenging.

Enhanced mossy fiber sprouting and synapse formation in organotypic hippocampal cultures following transient domoic acid excitotoxicity.

We have previously reported evidence of BDNF upregulation and increased neurogenesis in rat organotypic hippocampal slice cultures (OHSC) after a transient excitotoxic injury to the hippocampal CA1 area induced by low concentrations of the AMPA/kainate receptor agonist domoic acid (DOM). The changes observed in OHSC were consistent with observations in vivo, where low concentrations of DOM administered to rats during perinatal development caused increased BDNF and TrkB expression in the resulting adult animals. The in vivo low dose-DOM treatment also results in permanent alterations in hippocampal structure and function, including abnormal formation of dentate granule cell axons projecting to area CA3 (mossy fiber sprouting).

Brain vascular and hydrodynamic physiology.

Protecting the brain in vulnerable infants undergoing surgery is a central aspect of perioperative care. Understanding the link between blood flow, oxygen delivery, and oxygen consumption leads to a more informed approach to bedside care. In some cases, we need to consider how high we can let the partial pressure of carbon dioxide go before we have concerns about risk of increased cerebral blood volume and change in intracranial hydrodynamics.

Neuromuscular disorders: from diagnosis to translational research, drug development and clinical trials.

Pediatric neuromuscular disorders are a heterogeneous group of conditions that form four distinct groupings: (1) motor neuron diseases, (2) neuropathies, (3) disorders of the neuromuscular junction, and (4) myopathies.

Gaps and opportunities in refractory status epilepticus research in children: a multi-center approach by the Pediatric Status Epilepticus Research Group (pSERG).

Purpose: Status epilepticus (SE) is a life-threatening condition that can be refractory to initial treatment. Randomized controlled studies to guide treatment choices, especially beyond first-line drugs, are not available. This report summarizes the evidence that guides the management of refractory convulsive SE (RCSE) in children, defines gaps in our clinical knowledge and describes the development and works of the 'pediatric Status Epilepticus Research Group' (pSERG).

Transient domoic acid excitotoxicity increases BDNF expression and activates both MEK- and PKA-dependent neurogenesis in organotypic hippocampal slices.

Background: We have previously reported evidence of cell proliferation and increased neurogenesis in rat organotypic hippocampal slice cultures (OHSC) after a transient excitotoxic injury to the hippocampal CA1 area induced by low concentrations of the AMPA/kainate agonist domoic acid (DOM). An increased baseline rate of neurogenesis may contribute to recovery from DOM-induced mild injury but the intracellular mechanism(s) responsible for neuronal proliferation remain unclear. The current study investigated the key intracellular pathways responsible for DOM-induced neurogenesis in OHSC including the effects of transient excitotoxicity on the expression of brain-derived neurotrophic factor (BDNF), a well-known regulator of progenitor cell mitosis.

Differences in medical therapy goals for children with severe traumatic brain injury-an international study.

Objectives: To describe the differences in goals for their usual practice for various medical therapies from a number of international centers for children with severe traumatic brain injury.

Design: A survey of the goals from representatives of the international centers.

Setting: Thirty-two pediatric traumatic brain injury centers in the United States, United Kingdom, France, and Spain.

Pediatric intensive care treatment of uncontrolled status epilepticus.

The critically ill mechanically ventilated child with ongoing seizures that are refractory to any treatment presents a distinct challenge in pediatric neurocritical care. The evidence base from randomized controlled trials on which anti-epileptic drug (AED) strategy should be used is inadequate. This review of refractory and super-refractory status epilepticus summarizes recent pediatric case series regarding definitions, the second-tier AED therapies once initial anticonvulsants have failed, and the experience of high-dose midazolam, barbiturate anesthesia, and volatile anesthetics for uncontrolled status epilepticus.

Pediatric neurocritical care: a neurology consultation model and implication for education and training.

Pediatric neurocritical care is developing specialization within pediatric intensive care and pediatric neurology practice, and the evolving clinical expertise has relevance to training and education in both fields. We describe a model of service using a Neurology Consulting Team in the intensive care unit setting. Medical records were reviewed from a 32-month cohort of Neurology Consulting Team referrals.

Animal models of post-ischemic forced use rehabilitation: methods, considerations, and limitations.

Many survivors of stroke experience arm impairments, which can severely impact their quality of life. Forcing use of the impaired arm appears to improve functional recovery in post-stroke hemiplegic patients, however the mechanisms underlying improved recovery remain unclear. Animal models of post-stroke rehabilitation could prove critical to investigating such mechanisms, however modeling forced use in animals has proven challenging.

A novel approach to induction and rehabilitation of deficits in forelimb function in a rat model of ischemic stroke.

Aim: Constraint-induced movement therapy (CIMT), which forces use of the impaired arm following unilateral stroke, promotes functional recovery in the clinic but animal models of CIMT have yielded mixed results. The aim of this study is to develop a refined endothelin-1 (ET-1) model of focal ischemic injury in rats that resulted in reproducible, well-defined lesions and reliable upper extremity impairments, and to determine if an appetitively motivated form of rehabilitation (voluntary forced use movement therapy; FUMT) would accelerate post-ischemic motor recovery.

Methods: Male Sprague Dawley rats (3 months old) were given multiple intracerebral microinjections of ET-1 into the sensorimotor cortex and dorsolateral striatum.

Sleep apnoea in syndromic craniosynostosis occurs independent of hindbrain herniation.

Purpose: Hindbrain herniation (HH) is frequently found in syndromic craniosynostosis. It may cause impairment of the respiratory centres and manifest as sleep-disordered breathing. Our aim was to quantify sleep apnoea caused by HH in children with syndromic craniosynostosis.

From Lundberg to SIM-ICP: computational physiology and modeling intracranial pressure.

A simplified dynamic model generates patient-specific estimates of intracranial pressure and suggests a path forward for bringing simulated (SIM) physiologic models to the patient's bedside.

Seizures in 204 comatose children: incidence and outcome.

Purpose: Seizures are common in comatose children, but may be clinically subtle or only manifest on continuous electroencephalographic monitoring (cEEG); any association with outcome remains uncertain.

Methods: cEEG (one to three channels) was performed for a median 42 h (range 2-630 h) in 204 unventilated and ventilated children aged ≤15 years (18 neonates, 61 infants) in coma with different aetiologies. Outcome at 1 month was independently determined and dichotomized for survivors into favourable (normal or moderate neurological handicap) and unfavourable (severe handicap or vegetative state).

Enhanced neurogenesis in organotypic cultures of rat hippocampus after transient subfield-selective excitotoxic insult induced by domoic acid.

New neurons are continuously generated in the hippocampus and may play an important role in many physiological and pathological conditions. Here we present evidence of cell proliferation and neurogenesis after a selective and transient excitotoxic injury to the hippocampal cornu ammonis 1 (CA1) area induced by low concentrations of domoic acid (DOM) in rat organotypic hippocampal slice cultures (OHSC). DOM is an excitatory amino acid analog to kainic acid that acts through glutamate receptors to elicit a rapid and potent excitotoxic response.