Hematopoietic Endothelial Progenitor cells enhance motor function and cortical motor map integrity following cerebral ischemia.

Background: Hematopoietic stem cells (HSC) are recruited to ischemic areas in the brain and contribute to improved functional outcome in animals. However, little is known regarding the mechanisms of improvement following HSC administration post cerebral ischemia. To better understand how HSC effect post-stroke improvement, we examined the effect of HSC in ameliorating motor impairment and cortical dysfunction following cerebral ischemia.

Traumatic Brain Injury Alters the Trajectory of Age-Related Mitochondrial Change.

Background: Some epidemiologic studies associate traumatic brain injury (TBI) with Alzheimer's disease (AD).

Objective: To test whether a TBI-induced acceleration of age-related mitochondrial change could potentially mediate the reported TBI-AD association.

Methods: We administered unilateral controlled cortical impact (CCI) or sham injuries to 5-month-old C57BL/6J and tau transgenic rTg4510 mice.

Corticocortical connections of the rostral forelimb area in rats: a quantitative tract-tracing study.

The rostral forelimb area (RFA) in the rat is a premotor cortical region based on its dense efferent projections to primary motor cortex. This study describes corticocortical connections of RFA and the relative strength of connections with other cortical areas. The goal was to provide a better understanding of the cortical network in which RFA participates, and thus, determine its function in sensorimotor behavior.

Photoacoustic imaging of squirrel monkey cortical responses induced by peripheral mechanical stimulation.

Non-human primates (NHPs) are crucial models for studies of neuronal activity. Emerging photoacoustic imaging modalities offer excellent tools for studying NHP brains with high sensitivity and high spatial resolution. In this research, a photoacoustic microscopy (PAM) device was used to provide a label-free quantitative characterization of cerebral hemodynamic changes due to peripheral mechanical stimulation.

Spared Premotor Areas Undergo Rapid Nonlinear Changes in Functional Organization Following a Focal Ischemic Infarct in Primary Motor Cortex of Squirrel Monkeys.

Recovery of motor function after stroke is accompanied by reorganization of movement representations in spared cortical motor regions. It is widely assumed that map reorganization parallels recovery, suggesting a causal relationship. We examined this assumption by measuring changes in motor representations in eight male and six female squirrel monkeys in the first few weeks after injury, a time when motor recovery is most rapid.

Stimulation-Evoked Effective Connectivity (SEEC): An in-vivo approach for defining mesoscale corticocortical connectivity.

Background: Cortical electrical stimulation is a versatile technique for examining the structure and function of cortical regions and for implementing novel therapies. While electrical stimulation has been used to examine the local spread of neural activity, it may also enable longitudinal examination of mesoscale interregional connectivity.

New Method: Here, we sought to use intracortical microstimulation (ICMS) in conjunction with recordings of multi-unit action potentials to assess the mesoscale effective connectivity within sensorimotor cortex.

Reorganization of Ventral Premotor Cortex After Ischemic Brain Injury: Effects of Forced Use.

Background: Physical use of the affected upper extremity can have a beneficial effect on motor recovery in people after stroke. Few studies have examined neurological mechanisms underlying the effects of forced use in non-human primates. In particular, the ventral premotor cortex (PMV) has been previously implicated in recovery after injury.

Photoacoustic imaging of squirrel monkey cortical and subcortical brain regions during peripheral electrical stimulation.

The investigation of neuronal activity in non-human primate models is of critical importance due to their genetic similarity to human brains. In this study, we tested the feasibility of using photoacoustic imaging for the detection of cortical and subcortical responses due to peripheral electrical stimulation in a squirrel monkey model. Photoacoustic computed tomography and photoacoustic microscopy were applied on squirrel monkeys for real-time deep subcortical imaging and optical-resolution cortical imaging, respectively.

A cortical injury model in a non-human primate to assess execution of reach and grasp actions: implications for recovery after traumatic brain injury.

Background: Technological advances in developing experimentally controlled models of traumatic brain injury (TBI) are prevalent in rodent models and these models have proven invaluable in characterizing temporal changes in brain and behavior after trauma. To date no long-term studies in non-human primates (NHPs) have been published using an experimentally controlled impact device to follow behavioral performance over time.

New Method: We have employed a controlled cortical impact (CCI) device to create a focal contusion to the hand area in primary motor cortex (M1) of three New World monkeys to characterize changes in reach and grasp function assessed for 3 months after the injury.

Unrepaired decompressive craniectomy worsens motor performance in a rat traumatic brain injury model.

Decompressive craniectomy (DC) is often required to manage rising intracranial pressure after traumatic brain injury (TBI). Syndrome of the trephine (SoT) is a reversible neurologic condition that often occurs following DC as a result of the unrepaired skull. The purpose of the present study is to characterize neurological impairment following TBI in rats with an unrepaired craniectomy versus rats with a closed cranium.

Manifestations of Apprehension and Anxiety in a Sprague Dawley Cranial Defect Model.

Background: Syndrome of the trephined is a neurologic condition that commonly arises in patients who undergo craniectomy and have a prolonged cranial defect. Symptoms of this condition include headache, difficulties concentrating, diminished fine motor/dexterity skills, mood changes, and anxiety/apprehension. The authors hypothesize that an animal model demonstrating anxiety/apprehension in rats who undergo craniectomy is feasible utilizing standardized animal behavioral testing.

A Brain-Spinal Interface (BSI) System-on-Chip (SoC) for Closed-Loop Cortically-Controlled Intraspinal Microstimulation.

This paper reports on a fully miniaturized brain-spinal interface (BSI) system for closed-loop cortically-controlled intraspinal microstimulation (ISMS). Fabricated in AMS 0.35μm two-poly four-metal complementary metal-oxide-semiconductor (CMOS) technology, this system-on-chip (SoC) measures ~ 3.

Reversibility of Murine Motor Deficits Following Hemi-Craniectomy and Cranioplasty.

Background: Hemi-craniectomy is a common surgical procedure which allows the brain to swell and herniate and is often utilized to treat traumatic brain injury. When left untreated the scalp skin typically sinks on the side of the craniectomy creating a phenotype termed "sinking skin flap syndrome." In addition, these same patients often develop long-term neurocognitive deficits termed "syndrome of the trephined" as a result of their craniectomy which reverse when the cranial skull is replaced.

Cortical control of intraspinal microstimulation: Toward a new approach for restoration of function after spinal cord injury.

Approximately 6 million people in the United States are currently living with paralysis in which 23% of the cases are related to spinal cord injury (SCI). Miniaturized closed-loop neural interfaces have the potential for restoring function and mobility lost to debilitating neural injuries such as SCI by leveraging recent advancements in bioelectronics and a better understanding of the processes that underlie functional and anatomical reorganization in an injured nervous system. This paper describes our current progress toward developing a miniaturized brain-machine-spinal cord interface (BMSI) that converts in real time the neural command signals recorded from the cortical motor regions to electrical stimuli delivered to the spinal cord below the injury level.

Effects of Subdural Monopolar Cortical Stimulation Paired With Rehabilitative Training on Behavioral and Neurophysiological Recovery After Cortical Ischemic Stroke in Adult Squirrel Monkeys.

Background: Cortical stimulation (CS) combined with rehabilitative training (RT) has proven effective for enhancing poststroke functional recovery in rats, but human clinical trials have had mixed outcomes.

Objective: To assess the efficacy of CS/RT versus RT in a nonhuman primate model of cortical ischemic stroke.

Methods: Squirrel monkeys learned a pellet retrieval task, then received an infarct to the distal forelimb (DFL) representation of primary motor cortex.

Output Properties of the Cortical Hindlimb Motor Area in Spinal Cord-Injured Rats.

The purpose of this study was to examine neuronal activity levels in the hindlimb area of motor cortex following spinal cord injury (SCI) in rats and compare the results with measurements in normal rats. Fifteen male Fischer-344 rats received a 200 Kdyn contusion injury in the thoracic cord at level T9-T10. After a minimum of 4 weeks following SCI, intracortical microstimulation (ICMS) and single-unit recording techniques were used in both the forelimb and hindlimb motor areas (FLA, HLA) under ketamine anesthesia.

Effects of postinfarct myelin-associated glycoprotein antibody treatment on motor recovery and motor map plasticity in squirrel monkeys.

Background And Purpose: New insights into the brain's ability to reorganize after injury are beginning to suggest novel restorative therapy targets. Potential therapies include pharmacological agents designed to promote axonal growth. The purpose of this study was to test the efficacy of one such drug, GSK249320, a monoclonal antibody that blocks the axon outgrowth inhibition molecule, myelin-associated glycoprotein, to facilitate recovery of motor skills in a nonhuman primate model of ischemic cortical damage.

Towards a miniaturized brain-machine-spinal cord interface (BMSI) for restoration of function after spinal cord injury.

Nearly 6 million people in the United States are currently living with paralysis in which 23% of the cases are related to spinal cord injury (SCI). Miniaturized closed-loop neural interfaces have the potential for restoring function and mobility lost to debilitating neural injuries such as SCI by leveraging recent advancements in bioelectronics and a better understanding of the processes that underlie functional and anatomical reorganization in an injured nervous system. This paper describes our current progress towards developing a miniaturized brain-machine-spinal cord interface (BMSI) that is envisioned to convert in real time the neural command signals recorded from the brain to electrical stimuli delivered to the spinal cord below the injury level.

Rehabilitative training promotes rapid motor recovery but delayed motor map reorganization in a rat cortical ischemic infarct model.

Background: In preclinical stroke models, improvement in motor performance is associated with reorganization of cortical motor maps. However, the temporal relationship between performance gains and map plasticity is not clear.

Objective: This study was designed to assess the effects of rehabilitative training on the temporal dynamics of behavioral and neurophysiological endpoints in a rat model of focal cortical infarct.

Restoration of function after brain damage using a neural prosthesis.

Neural interface systems are becoming increasingly more feasible for brain repair strategies. This paper tests the hypothesis that recovery after brain injury can be facilitated by a neural prosthesis serving as a communication link between distant locations in the cerebral cortex. The primary motor area in the cerebral cortex was injured in a rat model of focal brain injury, disrupting communication between motor and somatosensory areas and resulting in impaired reaching and grasping abilities.

Reliability in the location of hindlimb motor representations in Fischer-344 rats: laboratory investigation.

Object: The purpose of the present study was to determine the feasibility of using a common laboratory rat strain for reliably locating cortical motor representations of the hindlimb.

Methods: Intracortical microstimulation techniques were used to derive detailed maps of the hindlimb motor representations in 6 adult Fischer-344 rats.

Results: The organization of the hindlimb movement representation, while variable across individual rats in topographic detail, displayed several commonalities.

Motor representations in the intact hemisphere of the rat are reduced after repetitive training of the impaired forelimb.

Background: During recovery from a unilateral cortical stroke, spared cortical motor areas in the contralateral (intact) cerebral cortex are recruited. Preclinical studies have demonstrated that compensation with the less-impaired limb may have a detrimental inhibitory effect on the intact cortical hemisphere and could impede recovery of the more-impaired limb. However, evidence from detailed neurophysiological mapping studies in animal models is lacking.

Gene expression changes of interconnected spared cortical neurons 7 days after ischemic infarct of the primary motor cortex in the rat.

After cortical injury resulting from stroke, some recovery can occur and may involve spared areas of the cerebral cortex reorganizing to assume functions previously controlled by the damaged cortical areas. No studies have specifically assessed gene expression changes in remote neurons with axonal processes that terminate in the infarcted tissue, i.e.