Thienylphencyclidine protection for the spinal cord of adult rats against extension of lesions secondary to a photochemical injury

“…Among different species, rats have been widely used as the model of choice to investigate the molecular and cellular mechanisms of changes in the basic neurochemistry after neurotrauma and the efficacy of pharmacological treatments, in order to attenuate the neuronal and glial damage leading to permanent functional impairment Brewer et al, 1999;Faden et al, 1988;Gaviria et al, 2000a,b;Pencalet et al, 1993;Ray et al, 1999;Rosenberg et al, 1999;Wrathall et al, 1994Wrathall et al, , 1996. Pharmacological intervention for neuroprotection soon after injury presents a promising therapeutic strategy, and some of the principal biochemical targets of the secondary injury mechanism have been identified in experimental models Cauquil-Caubere et al, 1999;Gaviria et al, 2000a,b;Rosenberg et al, 1999;Wrathall et al, 1994).…”

Section: Introduction E Xperimen Tal Models Of Spinal Cord Injury (Sci)mentioning

confidence: 99%

A Mouse Model of Acute Ischemic Spinal Cord Injury

Gaviria

Haton

Sandillon

et al. 2002

Journal of Neurotrauma

Self Cite

View full text Add to dashboard Cite

Mice models of spinal cord injury (SCI) should improve our knowledge of the mechanisms of injury and repair of the nervous tissue. They represent a powerful tool for the development of therapeutic strategies in the fields of pharmacological, cellular, and genetic approaches of neurotrauma. We demonstrate here that the photochemical graded ischemic spinal cord injury model, described in rats, can be successfully adapted in mice, in a reliable and reproducible manner. Following the intravenous injection of Rose Bengal, the translucent dorsal surface of the T9 vertebral laminae of C57BL/6 female mice was irradiated with a 560-nm wavelength-light (3-8 min depending on the experimental group). Animals were sacrificed at 1 day or 7 days after injury. Functional tests were performed daily for motor, sensory, autonomic, and reflex responses. Lesion histopathology was assessed for lesion length, percentage of residual white matter, and astrocytic reactivity. Experimental groups demonstrated a functional deficit, which was correlated to the increase of the irradiation time and, therefore, to the severity of the injury. Histopathological and immunocytochemical data were reliable morphological measurements characterizing the degree of injury, which were strongly correlated to the severity of the functional impairment. Despite differences in the mechanism of injury, the wound healing response described in other traumatic SCI mice models was confirmed (no cavitation and, conversely, the formation of a dense connective tissue matrix). In this context, the precise understanding of the mechanisms of healing response after SCI in mice and of neurochemical kinetics appear to be crucial in the development of therapeutic strategies of CNS repair. Thus, the possible use of an increasing collection of transgenic mice offers a new dimension for experimental research in this area. The ischemic photochemical model of SCI in mice represents a relevant model that can play a key role in this new era of neurotrauma research.

show abstract

“…Assessed in vitro at a flow rate of 1 µl.min -1 , this drug significantly crossed the dialysis membrane (recovery exceeded 20% in 3 hours) and was thus used in vivo in the same conditions (not shown). This drug is derived from 1-[1-(2-thienyl)cyclohexyl]piperidine (TCP), a potent NMDA antagonist (Rondouin et al, 1988;Pencalet et al, 1993), but is devoid of any glutamate antagonist activity. Treatment of the animals began 1 hour before the glutamate stimulation, was maintained during the 1 hour stimulation and lasted up to 1 hour after the glutamate.…”

Section: Methodsmentioning

confidence: 99%

Recurrent glutamate stimulations potentiate the hydroxyl radicals response to glutamate

et al. 1999

Self Cite

View full text Add to dashboard Cite

Neurotoxicity induced by hydroxyl radicals (OH) release is thought to be involved in a number of acute and chronical neuropathologies of the central nervous system. As far as neurodegenerative processes are concerned, the possible mechanisms giving rise to such OH releases remain poorly understood. In the present study, unanesthetized rats were perfused with a low salicylate solution through a chronic microdialysis cannula implanted into the striatum, and the OH responses to glutamate were analyzed. A single bolus of 3 mM glutamate elicited only minute releases of OH in naive rats. By contrast, recurrent infusions at 1-week intervals of the same glutamate concentration induced a robust OH response. Similar potentiation of the initial response also occurred for a larger glutamate concentration (30 mM). Oppositely, multiple injections of a high (300 mM) glutamate concentration resulted in a slow down of the initial OH response recorded in naive animals. The mechanisms giving rise to such effects are presently unknown. It is, however, clear that repetitive dysfunctions of the glutamate neurotransmission may be sufficient to promote the release of significant amounts of hydroxyl radicals, resulting in a progressive impairment of the astrocytic glutamate transporter, leading to neurodegenerative processes.

show abstract

Thienylphencyclidine protection for the spinal cord of adult rats against extension of lesions secondary to a photochemical injury

Cited by 28 publications

References 28 publications

Effects of citicoline on experimental spinal cord injury

Effects of citicoline on experimental spinal cord injury

A Mouse Model of Acute Ischemic Spinal Cord Injury

Recurrent glutamate stimulations potentiate the hydroxyl radicals response to glutamate

Contact Info

Product

Resources

About