Motor cortical neuronal hyperexcitability associated with α-synuclein aggregation.

ΑBSTRACT: In Parkinson's disease (PD), Lewy pathology deposits in the cerebral cortex, but how the pathology disrupts cortical circuit integrity and function remains poorly understood. To begin to address this question, we injected α-synuclein (αSyn) preformed fibrils (PFFs) into the dorsolateral striatum of mice to seed αSyn pathology in the cortical cortex and induce degeneration of midbrain dopaminergic neurons. We reported that αSyn aggregates accumulate in the motor cortex in a layer- and cell-subtype-specific pattern.

Sub-second characterization of locomotor activities of mouse models of Parkinsonism.

The degeneration of midbrain dopamine (DA) neurons disrupts the neural control of natural behavior, such as walking, posture, and gait in Parkinson's disease. While some aspects of motor symptoms can be managed by dopamine replacement therapies, others respond poorly. Recent advancements in machine learning-based technologies offer opportunities for unbiased segmentation and quantification of natural behavior in both healthy and diseased states.

Motor Cortical Neuronal Hyperexcitability Associated with α-Synuclein Aggregation.

Dysfunction of the cerebral cortex is thought to underlie motor and cognitive impairments in Parkinson disease (PD). While cortical function is known to be suppressed by abnormal basal ganglia output following dopaminergic degeneration, it remains to be determined how the deposition of Lewy pathology disrupts cortical circuit integrity and function. Moreover, it is also unknown whether cortical Lewy pathology and midbrain dopaminergic degeneration interact to disrupt cortical function in late-stage.

Motor Cortical Neuronal Hyperexcitability Associated with α-Synuclein Aggregation.

Dysfunction of the cerebral cortex is thought to underlie motor and cognitive impairments in Parkinson disease (PD). While cortical function is known to be suppressed by abnormal basal ganglia output following dopaminergic degeneration, it remains to be determined how the deposition of Lewy pathology disrupts cortical circuit integrity and function. Moreover, it is also unknown whether cortical Lewy pathology and midbrain dopaminergic degeneration interact to disrupt cortical function in late-stage.

Assessing outcomes in traumatic brain injury: Helsinki score versus Glasgow coma scale.

Background: The precision of assessment and prognosis in traumatic brain injury (TBI) is paramount for effective triage and informed therapeutic strategies. While the Glasgow Coma Scale (GCS) remains the cornerstone for TBI evaluation, it overlooks critical primary imaging findings. The Helsinki Score (HS), a novel tool designed to incorporate radiological data, offers a promising approach to predicting TBI outcomes.

Open-source platform for kinematic analysis of mouse forelimb movement.

Here we present an open-source behavioral platform and software solution for studying fine motor skills in mice performing reach-to-grasp task. We describe steps for assembling the box, training mice to perform the task, and processing the video with the custom software pipeline to analyze forepaw kinematics. The behavioral platform uses readily available and 3D-printed components and was designed to be affordable and universally reproducible.

Lestaurtinib (CEP-701) reduces the duration of limbic status epilepticus in periadolescent rats.

Background: The timely abortion of status epilepticus (SE) is essential to avoid brain damage and long-term neurodevelopmental sequalae. However, available anti-seizure treatments fail to abort SE in 30% of children. Given the role of the tropomyosin-related kinase B (TrkB) receptor in hyperexcitability, we investigated if TrkB blockade with lestaurtinib (CEP-701) enhances the response of SE to a standard treatment protocol and reduces SE-related brain injury.

Epidural Posterior Insular Stimulation Alleviates Neuropathic Pain Manifestations in Rats With Spared Nerve Injury Through Endogenous Opioid System.

Objectives: Neuropathic pain (NP) is defined as constant disabling pain secondary to a lesion or disease of the somatosensory nervous system. This condition is particularly difficult to treat because it often remains resistant to most treatment strategies. Despite the recent diversification of neurostimulation methods, some patients still suffer from refractory pain syndromes.

Somatosensory Thalamic Activity Modulation by Posterior Insular Stimulation: Cues to Clinical Application Based on Comparison of Frequencies in a Cat Model.

Background: The posterior insula (PI) has been proposed as a potential neurostimulation target for neuropathic pain relief as it represents a key-structure in pain processing. However, currently available data remain inconclusive as to efficient stimulation parameters.

Objective: As frequency was shown to be the most correlated parameter to pain relief, this study aims to evaluate the potential modulatory effects of low frequency (LF-IS, 50 Hz) and high-frequency (HF-IS, 150 Hz) posterior insular stimulation on the activity of somatosensory thalamic nuclei.