Biology subjects

Mohammadshirazi, A.

Publications and source records attributed to Mohammadshirazi, A..

3 recordsLinked to original sources

bioRxiv2024

An electrophysiological study about the pharmacological manipulation of the immediate consequences of a spinal trauma reveals a crucial role for TRPV4 antagonism.

A physical trauma to the spinal cord produces an immediate massive depolarizing injury potential accompanied both by a transient episode of spinal hypoxia, and an extensive cell loss at the level of injury, which interrupts conduction of longitudinal input along white matter tracts. Afterwards, the transient hypotonia and areflexia characterize the following spinal shock phase. The relationship between the extent of injury potentials and spinal cord injury (SCI) progression, as well as the potential pharmacological modulation of the immediate consequences of a trauma, have not yet been explored. To limit the peak of injury potentials and speed up recovery of reflex motor responses, we serially applied selective neurochemicals in the exact moment of an experimental physical trauma delivered through a calibrated device impacting the mid-thoracic cord of an entire CNS preparation of neonatal rats. Continuous lumbar root recordings monitored baseline DC-levels and reflex responses elicited by trains of electric pulses applied to sacrocaudal afferents. In uninjured preparations, each agent showed distinct effects on baseline polarization, modulation of synaptic responses, and appearance of bursting activity. Interestingly, neurochemicals acting on glutamatergic-, adenosinergic-, glycinergic- or GABAergic receptors, did not affect the monitored outcome when each parameter was normalized against pre-injury values. Conversely, the selective TRPV4 antagonist, RN1734, unlike the TRPA1 antagonist, AP18, reduced peak of injury potentials and speeded up full recovery of reflex responses within 1 min from trauma. Similarly, blockage of gap junctions quickly, yet partially, restored motor reflexes, while antagonism of GABAA receptors restored full reflexes, though slightly later. The current study indicates that both mechanosensitive TRPV4 receptors and GABAergic transmission reduce the immediate pathological consequences of a trauma when applied at the moment of impact, envisaging a clinical translation for preventing accidental spinal lesions during the most delicate spinal surgeries.

neuroscience↗

bioRxiv2024

A focal traumatic injury to the spinal cord causes an immediate and massive spreading depolarization sustained by chloride ions, with transient network dysfunction and remote cortical glia changes.

In clinics, physical injuries to the spinal cord cause a temporary motor areflexia below lesion, known as spinal shock. This topic is still underexplored due to the lack of preclinical SCI models that do not use anesthesia, which would affect spinal excitability. Our innovative design considered a custom-made micro impactor that provides localized and calibrated strikes to the ventral surface of the thoracic spinal cord of the entire CNS isolated from neonatal rats. Before and after injury, multiple ventral root (VR) recordings continuously traced respiratory rhythm, baseline spontaneous activities, and electrically-induced reflex responses. As early as 200 ms after impact, an immediate transient depolarization spread from the injury site to the whole spinal cord with distinct segmental velocities. Stronger strikes induced higher potentials causing, at the site of injury, a transient drop in tissue oxygen levels and a massive cell death with complete disconnection of longitudinal tracts. Below the impact site, expiratory rhythm and spontaneous lumbar activity were suppressed. On lumbar VRs, reflex responses transiently halted but later recovered to control values, while electrically-induced fictive locomotion remained perturbed. Moreover, low-ion modified Krebs solutions differently influenced impact-induced depolarizations, the magnitude of which amplified in low-Cl-. Moreover, remote changes in cortical glia occurred soon after spinal damage. Overall, our novel in vitro platform traces the immediate functional consequences of impacts to the spinal cord during development. This basic study provides insights on the SCI pathophysiology, unveiling an immediate chloride dysregulation and transient remote glial changes in the cortex.

neuroscience↗

bioRxiv2022

A novel preparation of the entire isolated CNS unveils the modulatory influences of supra-pontine structures on brainstem and spinal networks.

Several spinal motor output and essential rhythmic behaviors are controlled by supraspinal structures. Although of great advantage in deciphering their functional organization, existing preparations of the isolated brainstem and spinal networks only focus on local circuitry. The goal of our study has been to better characterize the contribution of higher centers to the neuronal networks involved in respiration and locomotion. Thus, a novel in vitro preparation from the isolated CNS of neonatal rodents was introduced to simultaneously record a stable respiratory rhythm from both cervical and lumbar ventral roots (VRs). Selective electrical pulses supplied to the pons and medulla evoked distinct VR responses in rostrocaudal direction with a staggered onset, while stimulation of ventrolateral medulla resulted in higher events from homolateral VRs. Moreover, electrical stimulation of a lumbar dorsal root (DR) elicited responses even from cervical VRs, albeit small and delayed, confirming functional ascending pathways. Furthermore, prototypical fictive locomotion was induced by trains of pulses applied to either the ventrolateral medulla or a DR. By progressively removing higher centers, duration of respiratory burst was reduced after a precollicular decerebration, which also affected the area of lumbar DR and VR potentials elicited by DR stimulation while frequency of respiration increased after a following pontobulbar transection. Keeping legs attached to the CNS allows for expressing the respiratory rhythm during peripheral stimulation of limbs. The study demonstrates that supra-pontine centers regulate the spontaneous respiratory rhythm, as well as electrically-evoked reflexes and spinal network activity. Thus, the current approach contributes to clarifying the modulatory influence of the brain on the brainstem and spinal micro-circuits.

neuroscience↗