Naslov
Studies of spinal locomotor networks in vitro: lessons from experimental damage and neuroprotection

Autori
Chiara Mattioli

Vrsta, podvrsta i kategorija rada
Ocjenski radovi, diplomski rad, diplomski

Fakultet
Università degli studi di Trieste

Mjesto
Trieste

Datum
20.09

Godina
2009

Stranica
31

Mentor
Mladinić Pejatović, Miranda

Ključne riječi
spinal cord injury; locomotion; in vitro spinal cord injury model; neuroprotection; magnesium

Sažetak
An acute injury to the spinal cord produces profound metabolic perturbation that extends and exacerbates tissue damage. Recent clinical trials to treat this condition with i.v. Mg2+ to maintain its extracellular concentration to standard levels provided disappointing results. The present study used an in vitro spinal cord model from the neonatal rat to investigate the role of extracellular Mg2+ in the lesion evoked by a pathological medium mimicking the metabolic perturbation (hypoxia, aglycemia, oxidative stress, acid pH) occurring in vivo. Damage was measured by taking as outcome locomotor network activity up to 24 h after primary insult. Pathological medium in 1 mM Mg2+ solution (1 h) largely depressed spinal reflexes and suppressed fictive locomotion on the same and the following day. Conversely, pathological medium in either Mg2+-free or 5 mM Mg2+ solution evoked temporary network depression and enabled fictive locomotion the day after. While global cell death was similar regardless od extracellular Mg2+ solution, white matter was particularly affected. In ventral horn the number of surviving neurons was the highest in Mg2+-free solution and the lowest in 1mM mg2+, while motoneurons were unaffected. These results indicate that preserving Mg2+ homeostasis has negative effects on experimental spinal injury. Furthermore, analyzing ventral horn neuron numbers in relation to fictive locomotion expression might provide a first estimate of the minimal size of the functional locomotor network. Treatments to block the pathophysiological processes triggered by acute spinal injury remain unsatisfactory as the underlying mechanisms are not completely understood. We investigated the feasibility of neuroprotection of lumbar locomotor networks by the glutamate antagonists CNQX and APV against a metabolic perturbation induced by the pathological medium or excitotoxicity expressed with kainite. Again, the study outcome was presence of fictive locomotion 24 h after the insult and its correlation with network histology. Inhibition of fictive locomotion by pathological medium was contrasted by simultaneous and even delayed (1 h later) co- application of CNQX and APV. Delayed neuroprotection was accompanied by increased survival of ventral horn premotoneurons and lateral column white matter. Neither CNQX nor APV alone provide neuroprotection. Kainate- mediated excitotoxicity always led to loss of fictive locomotion and extensive neuronal damage rather than white matter loss. CNQX and APV co-applied with kainite functually protected 1/3rd of preparations with improved motoneuron and dorsal horn neuronal counts, although they failed when their application was delayed. The present data indicate that locomotor network neuroprotection by canonical glutamate agonists was feasible if introduced very early during the pathological process of spinal injury. Hence, the present report provides a model not only for preclinical testing of novel neuroprotective agents but also for estimating the minimal network membership compatible with functional locomotor output.

Izvorni jezik
Engleski

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