Selective Targeting of a Defined Subpopulation of Corticospinal Neurons using a Novel Klhl14-Cre Mouse Line Enables Molecular and Anatomical Investigations through Development into Maturity.

The corticospinal tract (CST) facilitates skilled, precise movements, which necessitates that subcerebral projection neurons (SCPN) establish segmentally specific connectivity with brainstem and spinal circuits. Developmental molecular delineation enables prospective identification of corticospinal neurons (CSN) projecting to thoraco-lumbar spinal segments; however, it remains unclear whether other SCPN subpopulations in developing sensorimotor cortex can be prospectively identified in this manner. Such molecular tools could enable investigations of SCPN circuitry with precision and specificity.

Translating a Preclinically Tested 15 Hz rTMS Protocol to Humans With Chronic Spinal Cord Injury: A Safety and Feasibility Study.

Objectives: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation strategy with a demonstrated potential to reinforce the residual pathways after a spinal cord injury (SCI). A preclinically tested high-frequency (15 Hz) rTMS (15 Hz rTMS) protocol was shown to induce corticospinal tract axon regeneration growth and sprouting, resulting in improved voluntary motor control and performance. In a translational perspective, we aimed to investigate the safety and feasibility of the 15 Hz rTMS paradigm as an adjunct therapeutic intervention in individuals with chronic SCI.

A novel program including ride-on toys to improve upper extremity function in children with hemiplegia: a randomized controlled trial.

Objective: This study will assess the feasibility, acceptance, and preliminary efficacy of a novel and engaging task-oriented UE training program, Strength and Power in upper Extremities through Exploratory Driving (SPEED), including joystick-operated ride-on toys, as a therapy adjunct, to advance UE function among children with hemiplegia.

Methods: We will conduct a randomized controlled trial to compare SPEED training to a dose-matched program, Creative Rehabilitation for Arm Function Training (CRAFT), based on standard-of-care. 30 children with hemiplegia between 3 and 9 years will be recruited.

A vestibulospinal pathway for context-dependent motor control of the mouse tail.

Tail movement is critical for maintaining balance during locomotion in many animal species, yet its underlying neuromuscular control remains poorly understood. In this study, we investigate the neuronal substrates responsible for tail control in mice. Using high-resolution microCT and retrograde labeling, we describe the neuromuscular organization of the tail and identify distinct groups of motor neurons in the spinal cord that innervate proximal and distal muscles.

Joystick-Operated Ride-On Toys as a Therapy Adjunct for a Child With Hemiplegia: A Case Report.

Purpose: This case report describes the feasibility, acceptance, and satisfaction associated with community-based implementation of a novel upper extremity (UE) training program using a joystick-operated powered ride-on toy with an 8-year-old male child with unilateral cerebral palsy(UCP).

Summary Of Key Points: The 8-session, 1 month training program was feasible to implement in collaboration with the child's caregiver, was enjoyable and well-accepted by the child and his caregiver and associated with improvements in the child's affected UE motor function on participant-report and video-based measures.

Conclusion And Recommendations For Clinical Practice: Ride-on toys are versatile, easy-to-operate, family-friendly tools that can be used across a variety of naturalistic settings.

Neuropathic Pain-Like Responses in a Chronic CNS Injury Model Are Mediated by Corticospinal-Targeted Spinal Interneurons.

Chronic neuropathic pain is a persistent and debilitating outcome of traumatic central nervous system injury, affecting up to 80% of individuals. Postinjury pain is refractory to treatments due to the limited understanding of the brain-spinal cord circuits that underlie pain signal processing. The corticospinal tract (CST) plays critical roles in sensory modulation during skilled movements and tactile sensation; however, a direct role for the CST in injury-associated neuropathic pain is unclear.

Acute, not delayed, treatment of aflibercept enhances vessel density in post-ischemic brain and promotes long-term stroke recovery in obese mice.

Vascular comorbidities complicate stroke pathophysiology, worsen outcomes, and delay recovery. Obesity, in particular, significantly increases stroke-induced brain edema, a fatal complication during infarction, which leads to worsened long-term recovery. Treatment of aflibercept, a VEGF-trap, has been shown to reduce stroke-induced brain edema and attenuate acute neurological deficits in obese mice.

A seated virtual exercise program to improve cardiovascular function in adults with chronic neurological impairments: a randomized controlled trial.

Background: Individuals with chronic neurological impairments often face significant barriers to regular exercise such as limited access to facilities, transportation challenges, and safety concerns. Tele-exercise has emerged as a potential solution to these challenges, particularly in the context of the COVID-19 pandemic. This study aimed to investigate the effects of a seated home-based tele-exercise regimen on cardiovascular function in adults with chronic neurological impairments.

The dorsal column nuclei scale mechanical sensitivity in naive and neuropathic pain states.

During pathological conditions, tactile stimuli can aberrantly engage nociceptive pathways leading to the perception of touch as pain, known as mechanical allodynia. The brain stem dorsal column nuclei integrate tactile inputs, yet their role in mediating tactile sensitivity and allodynia remains understudied. We found that gracile nucleus (Gr) inhibitory interneurons and thalamus-projecting neurons are differentially innervated by primary afferents and spinal inputs.

Developmental molecular signatures define cortico-brainstem circuit for skilled forelimb movement.

Skilled movement relies on descending cortical projections to the brainstem and spinal cord. While corticospinal neurons (CSN) have long been recognized for their role in fine motor control, the contribution of cortical projections to the brainstem remains poorly understood. Here, we identify a previously unrecognized direct cortico-brainstem circuit that emerges early in development and persists into adulthood.

Conditioning Electrical Nerve Stimulation Enhances Functional Rewiring in a Mouse Model of Nerve Transfer to Treat Chronic Spinal Cord Injury.

Background/objectives: Nerve transfer surgery is a state-of-the-art surgical approach to restore hand and arm function in individuals living with tetraplegia, significantly impacting daily life. While nearly a third of all individuals with chronic spinal cord injury may benefit from this intervention, variability in outcomes can limit the functional impact. A bedside to bench approach was taken to address the variable response of tetraplegic individuals to nerve transfer surgery.

Spine plasticity to restore the cortical networks of movement: a therapeutic approach to spinal cord injury.

This scientific commentary refers to 'Edonerpic maleate enhances functional recovery from spinal cord injury with cortical reorganization in non-human primates', by Uramaru . (https://doi.org/10.

Impact of prior antiplatelet therapy on safety and efficacy of alteplase in acute ischemic stroke: a systematic review and meta-analysis.

Background: Intravenous thrombolysis (IVT), utilizing the clot-dissolving medications alteplase (rt-PA) or tenecteplase (TNK), is the cornerstone in acute ischemic stroke (AIS) emergency intervention. However, the impact of prior antiplatelet therapy (APT) on post-IVT outcomes when utilizing alteplase remains controversial. We conducted a systematic review and meta-analysis to evaluate the effect of prior APT on the outcomes after using alteplase in AIS patients.

Modulation of Extrinsic and Intrinsic Signaling Together with Neuronal Activation Enhances Forelimb Motor Recovery after Cervical Spinal Cord Injury.

Singular strategies for promoting axon regeneration and motor recovery after spinal cord injury (SCI) have been attempted with limited success. For instance, the deletion of and phosphatase and tensin homolog () (an extrinsic and intrinsic modulating factor, respectively) in corticospinal neurons (CSNs) promotes axon sprouting after thoracic SCI; however, it is unable to restore motor function. Here, we examine the effects of combining deletion in CSNs with chemogenetic neuronal stimulation on axonal growth and motor recovery after SCI in mice.

Ischemic Conditioning Promotes Transneuronal Survival and Stroke Recovery via CD36-Mediated Efferocytosis.

Background: Remote ischemic conditioning (RIC) has been implicated in cross-organ protection in cerebrovascular disease, including stroke. However, the lack of a consensus protocol and controversy over the clinical therapeutic outcomes of RIC suggest an inadequate mechanistic understanding of RIC. The current study identifies RIC-induced molecular and cellular events in the blood, which enhance long-term functional recovery in experimental cerebral ischemia.

Acute Extrinsic Activation of the RANKL Pathway Decreases Wound Healing and Functional Recovery After Spinal Cord Injury in Mice.

Manipulating wound healing-associated signaling after SCI presents a promising avenue for increasing the recovery of function after injury. This study explores the potential of targeting molecular regulators of wound healing, initially identified in nonneural tissues, to enhance outcomes after SCI. Astrocytes, pivotal in central nervous system wound healing, play a crucial role in tissue remodeling and recovery.

Selective Targeting of a Defined Subpopulation of Corticospinal Neurons using a Novel Klhl14-Cre Mouse Line Enables Molecular and Anatomical Investigations through Development into Maturity.

The corticospinal tract (CST) facilitates skilled, precise movements, which necessitates that subcerebral projection neurons (SCPN) establish segmentally specific connectivity with brainstem and spinal circuits. Developmental molecular delineation enables prospective identification of corticospinal neurons (CSN) projecting to thoraco-lumbar spinal segments; however, it remains unclear whether other SCPN subpopulations in developing sensorimotor cortex can be prospectively identified in this manner. Such molecular tools could enable investigations of SCPN circuitry with precision and specificity.

A Kinematic Deviation Index (KDI) for Evaluation of Forelimb Function in Rodents.

Rodent models are widely used to study neurological conditions and assess forelimb movement to measure function performance, deficit, recovery and treatment effectiveness. Traditional assessment methods based on endpoints such as whether the task is accomplished, while easy to implement, provide limited information on movement patterns important to assess different functional strategies. On the other side, detailed kinematic analysis provides granular information on the movement patterns but is difficult to compare across laboratories, and may not translate to clinical metrics of upper limb function.

Quantitative patterns of visual impairment and recovery in children with brain injury.

Brain injury can cause many distinct types of visual impairment in children, but these deficits are difficult to quantify due to co-morbid deficits in communication and cognition. Clinicians must instead rely on low-resolution, subjective judgements of simple reactions to handheld stimuli, which limits treatment potential. We have developed an interactive assessment program called the Visual Ladder, which uses gaze-based responses to intuitive, game-like tasks to address the lack of broad-spectrum quantified data on the visual abilities of children with brain injury.

Anatomical and functional analysis of the corticospinal tract in an FRDA mouse model.

Friedreich's ataxia (FRDA) is one of the most common hereditary ataxias. It is caused by a GAA repeat in the first intron of the FXN gene, which encodes an essential mitochondrial protein. Patients suffer from progressive motor dysfunction due to the degeneration of mechanoreceptive and proprioceptive neurons in dorsal root ganglia (DRG) and cerebellar dentate nucleus neurons, especially at early disease stages.

Forelimb motor recovery by modulating extrinsic and intrinsic signaling as well as neuronal activity after the cervical spinal cord injury.

Singular strategies for promoting axon regeneration and motor recovery after spinal cord injury (SCI) have been attempted with limited success. Here, we propose the combinatorial approach of deleting extrinsic and intrinsic factors paired with neural stimulation, will enhance adaptive axonal growth and motor recovery after SCI. We previously showed the deletion of and in corticospinal neurons inhibits axon dieback and promotes axon sprouting after lumbar SCI.

Differential expression of cellular prion protein (PrP) in mouse hepatitis virus induced neuroinflammation.

The cellular prion protein (PrP) is an extracellular cell membrane protein. Due to its diversified roles, a definite role of PrP has been difficult to establish. During viral infection, PrP has been reported to play a pleiotropic role.