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Background Acute Ischemic Stroke (AIS) represents an economic challenge for health systems all over the globe. Changes of neuroactive steroids have been found in different neurological diseases. We have previously demonstrated that old patients with AIS show changes of plasma cortisol and estradiol concentrations, in that increased steroid levels are associated with a deterioration of neurological status and a worse cognitive decline. Objective The present study assessed in patients with AIS if changes of behavior, Brain-Derived Neurotrophic Factor (BDNF) and Nitrites (NO-2) bear a relationship with the degree of hypercortisolism. Methods We recruited patients hospitalized within the first 24 hours of AIS. Subjects were divided into two groups, each one composed of 40 control subjects and 40 AIS patients, including men and women. The neurological condition was assessed using the National Institute of Health Stroke Scale (NIHSS) and the cognitive status with the Montreal Cognitive Assessment (MoCA). The emotional status was evaluated using the Montgomery-Asberg Depression Rating Scale (MADRS), whereas the Modified Rankin Scale (MRS) was used to determine the functional condition. BDNF and NO-2 plasma levels were measured by ELISA and the Griess reaction method, respectively. Results We found that in AIS patients, increased plasma cortisol was negatively correlated with plasma BDNF and NO-2 levels, neurological condition, cognition, functional responses and emotional status, suggesting a relationship between the declines of clinical, behavioral and blood parameters with stress-induced cortisol elevation. Conclusion Nitrites and BDNF may represent potential biomarkers for cortisol negative effects on the area of cerebral ischemia and penumbra, potentiating ischemic cell damage.

Despite several scientific and technological advances, there is no single neuroprotective treatment that can reverse the brain damage after acute ischemic stroke (AIS). Neuroactive steroids are cholesterol-derived hormones that have the ability to modulate the normal and pathologic nervous system employing genomic and nongenomic mechanisms. In this work, we first investigated if AIS affects the plasma concentration of 5 neuroactive steroids (cortisol, estradiol, progesterone, testosterone, and 3α-androstenediol glucuronide). Second, we studied if levels of circulating steroids associate with neurological, cognitive, and functional outcome in a cohort of 60- to 90 year-old male and female patients with AIS. For this purpose, we recruited patients who were hospitalized at the Emergency Room of the Central Military Hospital within the first 24 h after stroke onset. We designed 2 experimental groups, each one composed of 30 control subjects and 30 AIS patients, both males and females. The assessment of neurological deficit was performed with the NIHSS and the tests used for the functional and cognitive status were: (1) modified Rankin Scale; (2) Photo test, and (3) abbreviated Pfeiffer's mental status questionnaire. We observed a significant difference in plasma concentration of cortisol and estradiol between both experimental groups. In the AIS group, higher levels of these neuroactive steroids were associated with more pronounced neurological, cognitive and functional deficits in women compared to men. We propose that in elderly patients, high levels of circulating neuroactive steroids like cortisol and estradiol could potentiate AIS-mediated neuropathology in the ischemic and penumbra areas. Fil: Casas, Sebastian. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor ; Argentina Fil: Gonzalez Deniselle, Maria Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Gargiulo Monachelli, Gisella Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Pérez, Andrés Felipe. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor ; Argentina Fil: Tourreilles, Martin. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor ; Argentina Fil: Mattiazzi, Marcelo. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor ; Argentina Fil: Ojeda, Cristian. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor ; Argentina Fil: Lotero Polesel, Daniel. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor ; Argentina Fil: de Nicola, Alejandro Federico. Ministerio de Defensa. Ejército Argentino. Hospital Militar Central Cirujano Mayor ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina

There is a growing amount of evidence for a neuroprotective role of progesterone and its neuroactive metabolite, allopregnanolone, in animal models of neurodegenerative diseases. By using a model of hemiparkinsonism in male rats, injection of the neurotoxic 6-OHDA in left striatum, we studied progesterone's effects on rotational behavior induced by amphetamine or apomorphine. Also, in order to find potential explanatory mechanisms, we studied expression and activity of nigrostriatal 3α-hydroxysteroid oxidoreductase, the enzyme that catalyzes progesterone to its active metabolite allopregnanolone. Coherently, we tested allopregnanolone for a possible neuromodulatory effect on rotational behavior. Also, since allopregnanolone is known as a GABAA modulator, we finally examined the action of GABAA antagonist bicuculline. We found that progesterone, in addition to an apparent neuroprotective effect, also increased ipsilateral expression and activity of 3α-hydroxysteroid oxidoreductase. It was interesting to note that ipsilateral administration of allopregnanolone reversed a clear sign of motor neurodegeneration, that is, contralateral rotational behavior. A possible GABAA involvement modulated by allopregnanolone was shown by the blocking effect of bicuculline. Our results suggest that early administration of progesterone possibly activates genomic mechanisms that promote neuroprotection subchronically. This, in turn, could be partially mediated by fast, nongenomic, actions of allopregnanolone acting as an acute modulator of GABAergic transmission.

The hypothalamic release of glutamate and GABA regulates neurosecretory functions that may control the onset of puberty. This release may be influenced by neurosteroids such as allopregnanolone. Using superfusion experiments we examined the role of allopregnanolone on the K+-evoked and basal [3H]-glutamate and [3H]-GABA release from mediobasal hypothalamus and anterior preoptic area in prepubertal, vaginal opening and pubertal (P) rats and evaluated its modulatory effect on GABAA and NMDA (N-methyl-d-aspartic acid) receptors. Also, we examined the hypothalamic activity and mRNA expression of 3α-hydroxysteroid oxidoreductase (3α-HSOR) – enzyme that synthesizes allopregnanolone – using a spectrophotometric method and RT-PCR, respectively. Allopregnanolone increased both the K+-evoked [3H]-glutamate and [3H]-GABA release in P rats, being the former effect mediated by the modulation of NMDA receptors – as was reverted by Mg2+ and by the NMDA receptor antagonist AP-7 and the latter by the modulation of NMDA and GABAA receptors – as was reverted by Mg2+ and the GABAA receptor antagonist bicuculline. The neurosteroid also increased the basal release of [3H]-glutamate in VO rats in an effect that was dependent on the modulation of NMDA receptors as was reverted by Mg2+. On the other hand we show that allopregnanolone reduced the basal release of [3H]-GABA in P rats although we cannot elucidate the precise mechanism by which the neurosteroid exerted this latter effect. The enzymatic activity and the mRNA expression of 3α-HSOR were both increased in P rats regarding the other two studied stages of sexual development. These results suggest an important physiological function of allopregnanolone in the hypothalamus of the P rat where it might be involved in the ‘fine tuning’ of neurosecretory functions related to the biology of reproduction of the female rats. Fil: Giuliani, Fernando Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Instituto de Investigaciones Biomédicas. Universidad de Mendoza; Argentina Fil: Escudero, Carla Gimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Instituto de Investigaciones Biomédicas. Universidad de Mendoza; Argentina Fil: Casas, Sebastián Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Instituto de Investigaciones Biomédicas. Universidad de Mendoza; Argentina Fil: Bazzocchini, V.. Instituto de Investigaciones Biomédicas. Universidad de Mendoza; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Yunes, Roberto Miguel Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Instituto de Investigaciones Biomédicas. Universidad de Mendoza; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas- Area de Farmacologia; Argentina Fil: Laconi, Myriam Raquel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina Fil: Cabrera Kreiker, Ricardo Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina; Argentina

The reagent MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, a yellow tetrazole) is reduced to formazan in living cells, giving a purple colored product. The product absorbance issusceptible to be measured at a certain wavelength by a spectrophotometer. We report in this paper the use of MTT as a suitable method for checking both the viability of neural tissues as well as the correct location of stereotaxically placed cerebral cannulae. Evidence is given that this method can be useful not only because it is a new way of utilizing a vital staining to evaluate cannulae location, but also because MTT is a simple, effective and cheaper way of assessing the arousal level of neural tissues under study. In doing so, we can effectively test the stimulatory and/or inhibitory actions of several reagents in what we finally named as MTT-micro assay on living tissues: the MTT-malt. Fil: García, S.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina Fil: Nanfaro, F.. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina Fil: Casas, Sebastián Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Cabrera Kreiker, Ricardo Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Yunes, Roberto Miguel Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina

In this work we investigated how the neurosteroid allopregnanolone can modulate learning and memory processes. For this purpose, we used ovariectomized (OVX) rats subcutaneously injected with oestradiol benzoate (E) alone or E and progesterone (P). Then, rats were injected in dorsal hippocampus with allopregnanolone or vehicle. Animals were tested in inhibitory avoidance task (IA task). After behavioural test hippocampal mRNA expression and enzymatic activity of 3-HOR, the enzyme responsible of allopregnanolone synthesis, were analysed. In IA task OVX-EP rats spent less time on platform, compared to those OVX or OVX-E. Regression analyses revealed that there was a significant negative relationship between E-P infusion and performance in this task. Pre-training allopregnanolone administration to OVX-EP rats increased the time spent on the platform. Interestingly, when enzymatic activity of 3-HOR was tested, OVX-EP rats showed a significant decrease in the enzymatic activity, compared with OVX and OVX-E rats. In addition, OVX-EP group showed a significant increase in the enzymatic activity after intrahippocampal infusion of allopregnanolone. On the other hand, when mRNA expression of 3-HOR was analysed no differences were observed when the hippocampal allopregnanolone injection was done. These results suggest that E and P have amnesic effects on female rats, being reversed by allopregnanolone through its modulation on hippocampal 3-HOR activity. Fil: Escudero, Carla Gimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad de Mendoza; Argentina Fil: Casas, Sebastián Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad de Mendoza; Argentina Fil: Giuliani, Fernando Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad de Mendoza; Argentina Fil: Bazzocchini, Vanesa Silvana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad de Mendoza; Argentina Fil: García, Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad de Mendoza; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina Fil: Yunes, Roberto Miguel Federico. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina. Universidad de Mendoza; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Cabrera Kreiker, Ricardo Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad de Mendoza; Argentina

Hemiparkinsonisminduced by 6-hydroxydopamine (6-OHDA) injected in left corpus striatum is a recognized model of motor deficits in rats. Some reports concerning motor deficits indicate a favorable response to steroid administration in hemiparkinsonian animals. However, there is no much information regarding progesterone administration in relation to cognitive and affective dysfunctions. Here we could confirm earlier reports regarding a mild deficit of memory and a noticeable depressive-like behavior 4 weeks after injecting 6-OHDA. We also present some evidence that progesterone could be ? when administered 7 days after the injection of 6-OHDA ? a possible neuroprotector concerning both motor deficits as well as cognitive ? memory- and depression-like behaviors. The affective deficit was reverted by administering the tricyclic antidepressant imipramine. Since Parkinson´s disease is a conspicuous cause of psycho-organic decline in human beings, it would be important to be able of dealing early with non-motor indicators in order to use prospective neuroprotectors to prevent the progression of the disease Fil: Casas, Sebastián Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina Fil: García Menéndez, Sebastián Marcelo Manuel. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Cabrera Kreiker, Ricardo Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Nanfaro, Federico. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina Fil: Escudero, Carla Gimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina Fil: Yunes, Roberto Miguel Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentina

Ghrelin (Ghr) is a peptide produced peripherally and centrally. It participates in the modulation of different biological processes. In our laboratory we have shown that (a) Ghr administration, either intracerebroventricular or directly into the hippocampus enhanced memory consolidation in a step down test in rats (b) the effect of Ghr upon memory decreases in animals pretreated with a serotonin (5-HT) reuptake inhibitor, Fluoxetine, suggesting that Ghr effects in the hippocampus could be related to the availability of 5-HT. It has been demonstrated that Ghr inhibits 5-HT release from rat hypothalamic synaptosomes. Taking in mint these evidences, we studied the release of radioactive 5-HT to the superfusion medium from hippocampal slices treated with two doses of Ghr (0.3 and 3 nm/μl). Ghr inhibited significantly the 5-HT release in relation to those superfused with artificial cerebrospinal fluid (ACSF) (H = 9.48, df = 2, p ≤ 0.05). In another set of experiments, Ghr was infused into the CA1 area of hippocampus of the rats immediately after training in the step down test and the 5-HT release from slices was studied 24h after Ghr injection showing that in this condition also the 5-HT release was inhibited (H = 11.72, df = 1, p ≤ 0.05). In conclusion, results provide additional evidence about the neurobiological bases of Ghr action in hippocampus.