Biomedical subjects

M A Perez-Pinzon

Publications and source records attributed to M A Perez-Pinzon.

4 recordsLinked to original sources

PubMed2006

Estrogen preconditioning protects the hippocampal CA1 against ischemia.

Estrogen is neuroprotective against ischemia in both in vivo and in vitro injury models. Because of the promising preclinical data on neuroprotection, the Women's Estrogen for Stroke Trial was initiated. The outcomes from this trial were, however, unsuccessful and questions emerged about the safety of chronic estrogen treatment in women. In contrast to the chronic estrogen treatment strategy, the present study aims to investigate: (1) the neuroprotective efficacy of single estrogen pretreatment/preconditioning; and (2) the existence of a similarity between estrogen- and ischemic preconditioning-induced neuroprotection against cerebral ischemia. The efficacy of estrogen was tested in an in vitro model of cerebral ischemia using hippocampal organotypic slice culture system. The hippocampal organotypic slice cultures were generated from female neonatal (9-11 days old) Sprague-Dawley rats. The slices were exposed to estradiol-17beta (0.5, 1, 5 nM) for various durations (1, 2 or 4 h) 48 h prior to ischemia (40 min of oxygen-glucose deprivation). For ischemic preconditioning, slices were exposed to sublethal oxygen-glucose deprivation (15 min), 48 h prior to lethal oxygen-glucose deprivation. Quantification of cell death in hippocampal CA1 region was conducted by using propidium iodide fluorescence staining technique. Results demonstrated that estrogen preconditioning significantly protects the hippocampal CA1 region against ischemia (P<0.001) and mimicked ischemic preconditioning-induced neuroprotection. The propidium iodide fluorescence values of estrogen preconditioning, ischemic preconditioning and ischemia groups were 21+/-2 (mean+/-S.E.M.) (1 nM; 2 h; n=15), 18+/-2 (5 nM; 4 h; n=12), 32+/-3 (n=8), 65+/-3 (n=27), respectively. Further, estrogen preconditioning initiated a calcium-mediated signaling pathway leading to protection of CA1 neurons against ischemia. Future investigations in estrogen preconditioning may suggest new estrogen regimens that avoid potential side effects of chronic estrogen treatment for stroke patients.

Analysis of Variance↗

PubMed2000

Chronic failure in the maintenance of long-term potentiation following fluid percussion injury in the rat.

Traumatic brain injury (TBI) can produce chronic cognitive learning/memory deficits that are thought to be mediated, in part, by impaired hippocampal function. Experimentally induced TBI is associated with deficits in hippocampal synaptic plasticity (long-term potentiation, or LTP) at acute post-injury intervals but plasticity has not been examined at long-term survival periods. The present study was conducted to assess the temporal profile of LTP after injury and to evaluate the effects of injury severity on plasticity. Separate groups of rats were subjected to mild (1.1-1.4 atm), moderate (1.8-2.1 atm), or severe (2.2-2.7 atm) fluid percussion (FP) injury (or sham surgery) and processed for hippocampal electrophysiology in the first or eighth week after injury. LTP was defined as a lasting increase in field excitatory post-synaptic potential (fEPSP) slope in area CA1 following tetanic stimulation of the Schaffer collaterals. The fEPSP slope was measured for 60 min after tetanus. Assessment of LTP at the acute interval (6 days) revealed modest peak slope potentiation values (129-139%), which declined in each group (including sham) over the hour-long recording session and did not differ between groups. Eight weeks following injury, slices from all groups exhibited robust maximal potentiation (134-147%). Levels of potentiation among groups were similar at the 5-min test interval but differed significantly at the 30- and 60-min test intervals. Whereas sham slices showed stable potentiation for the entire 60-min assessment period, slices in all of the injury groups exhibited a significant decline in potentiation over this period. These experiments reveal a previously unknown effect of TBI whereby experimentally induced injury results in a chronic inability of the CA1 hippocampus to maintain synaptic plasticity. They also provide evidence that sham surgical procedures can significantly influence hippocampal physiology at the acute post-TBI intervals. The results have implications for the mechanisms underlying the impaired synaptic plasticity following TBI.

Animals↗

PubMed1999

Optical methods for probing mitochondrial function in brain slices.

Brain slice preparations have become useful tools for studying multiple facets of normal brain function and for investigations of brain pathophysiology. Recently, a variety of neurological disorders have been linked to dysfunction of brain mitochondria. In this report we discuss optical methods for probing mitochondrial function in brain slices. Absorption spectrophotometric and spectrofluorometric techniques are described for measuring changes in the redox activity of mitochondrial cytochromes and the primary respiratory chain substrate nicotinamide adenine dinucleotide (NADH), respectively. A spectrofluorometric method is described also for measuring changes in mitochondrial membrane potential using the potential-sensitive fluorescent indicator JC-1. These methods used together have proven to be useful for studying dysfunction of mitochondria following in vitro ischemia in hippocampal slices, and might also be valuable for investigations of mitochondrial involvement in other neurological disorders.

Animals↗

PubMed1997

SNX-111, a novel, presynaptic N-type calcium channel antagonist, is neuroprotective against focal cerebral ischemia in rabbits.

Cytosolic Ca2+ overload has been proposed as a main cause of neuronal injury during cerebral ischemia. SNX-111, a synthetic product of the naturally occurring omega-conotoxin MVIIA, is a novel, presynaptic N-type Ca2+ channel antagonist and has been reported to be neuroprotective against cerebral ischemia. We studied the neuroprotective effects of SNX-111 in a rabbit model of focal cerebral ischemia. New Zealand white male rabbits (2.5-3.5 kg) were given 1 mg/kg/h i.v. SNX-111 (n=8) or normal saline (n=8) 10 min after onset of a 2-h period of transient focal cerebral ischemia induced by occlusion of the left middle cerebral, anterior cerebral and internal carotid arteries followed by 4 h reperfusion. SNX-111 significantly attenuated overall cortical ischemic neuronal damage by 44% (saline, 38.7+/-3.0%; SNX-111, 21.5+/-6.0%, P<0.05) and regions of hyperintensity on T2-weighted MRI by 30% (saline, 70.6+/-4.0%; SNX-111, 49.3+/-11.0%, P<0.05). No significant difference in (regional cerebral blood flow) rCBF or MAP (mean arterial blood pressure) was found between SNX-111- and saline-treated rabbits suggesting that neuroprotection is due to a cellular effect. We conclude that SNX-111 reduces ischemic injury in this model. Its use as a clinical neuroprotective agent for cerebrovascular surgery or stroke should be investigated further.

Animals↗