Endothelial and neuronal nitric oxide synthase inhibitors influences angiotensin II pressor effect in central nervous system

The present study investigated the central role of angiotensin II and nitric oxide on arterial blood pressure (MAP) in rats. Losartan and PD123349 AT 1 and AT 2 (selective no peptides antagonists angiotensin receptors), as well as FK 409 (a nitric oxide donor), N W-nitro-L-arginine methyl ester (L-NAME) a constituve nitric oxide synthase inhibitor endothelial (eNOSI) and 7-nitroindazol (7NI) a specific neuronal nitric oxide synthase inhibitor (nNOSI) were used. Holtzman strain, (Rattus norvergicus) weighting 200-250 g were anesthetized with zoletil 50 mg kg -1 (tiletamine chloridrate 125 mg and zolazepan chloridrate 125 mg) into quadriceps muscle anda stainless steel cannula was stereotaxically implanted into their Lateral Ventricle (LV). Controls were injected with a 0.5 μl volume of 0.15 M NaCl. Angiotensin II injected into LV increased MAP (19±3 vs. control 3±1 mm Hg), which is potentiated by prior injection of L-NAME in the same site 26±2 mm Hg. 7NI injected prior to ANG II into LV also potentiated the pressor effect of ANG II but with a higher intensity than L-NAME 32±3 mm Hg. FK 409 inhibited the pressor effect of ANG II (6±1 mm Hg). Losartan injected into LV before ANG II influences the pressor effect of ANG II (8±1 mm Hg). The PD 123319 decreased the pressor effects of ANG II (16±1 mm Hg). Losartan injected simultaneously with FK 409 blocked the pressor effect of ANG II (3±1 mm Hg). L-NAME produced an increase in the pressor effect of ANG II, may be due to local vasoconstriction and all at once by neuronal NOS inhibition but the main effect is of the 7-NIT an specific nNOS inhibitor. The AT 1 antagonist receptors improve basal nitric oxide (NO) production and release. These data suggest the involvement of constitutive and neuronal NOS in the control of arterial blood pressure induced by ANG II centrally, evolving AT 1 receptor-mediated vasoconstriction and AT 2 receptor-mediated vasodilatation. These results were confirmed by the experiment using FK 409. © 2006 Asian Network for Scientific Information.

Intravascular lymphomatosis in the central nervous system of dogs: Immunohistochemical investigation in two cases

We report here two postmortem cases of dogs with intravascular lymphomatosis affecting the central nervous system. Intravascular lymphomatosis is represented by an exclusively intravascular proliferation of neoplastic lymphoid cells. To characterize the origin of the neoplastic cells, we have proceeded with immunohistochemical analysis to identify B and T lymphocytes and endothelial cells. The results showed predominance of cells from the T cell lineage, and no evidence of B cell origin was found. Few cells from one dog also exhibited cytoplasmatic staining for vimentin and Von Willebrand factor. Although in one case some immunophenotype diversity was observed, the massive presence of CD3 positive cells confirmed these neoplasms as intravascular lymphomatosis of T cell origin.

Neurotoxic action of permethrin in Rhipicephalus sanguineus (Latreille, 1806) (Acari: Ixodidae) female ticks. Morphological and cytochemical evaluation of the central nervous system

Studies on the molecular bases of the neurotoxic action of acaricides are found in the literature; but there are no studies of this action on the nervous system of ticks at the cellular level. The present study describes the morphological and cytochemical changes in the synganglion of Rhipicephalus sanguineus semi-engorged females exposed to different concentrations of permethrin, a pyrethroid with recognized neurotoxic action. Permethrin induced the degeneration of the synganglion through a process of apoptosis involving autophagy, characterized by the condensation and margination of the chromatin, formation of blebs in the nuclear envelope and fragmentation of the nucleus, loss of shape of neural cells and integrity of cellular membrane, cytoplasmic shrinkage, and lower levels of acid phosphatase in the nervous tissue as the concentration of permethrin increased. This study provided further evidence of the neurotoxic action of permethrin, which impairs the metabolism of R. sanguineus nervous systems, and consequently the physiology of other systems, dependent on the neural control. These results provide cytochemical and histological confirmation of the neurotoxic action of permethrin, previously inferred from molecular and tick behavioral evidence. © 2013 Elsevier B.V.

Pyridinic analog of the natural product (-)-spectaline as potential adjuvant for the treatment of central nervous system disorders

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Facilitation of breathing by leptin effects in the central nervous system

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Central nitrergic system regulation of neuroendocrine secretion, fluid intake and blood pressure induced by angiotensin-II

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Porencephaly and cortical dysplasia as cause of seizures in a dog

Background: Seizures are a common problem in small animal neurology and it may be related to underlying diseases. Porencephaly is an extremely rare disorder, and in Veterinary Medicine it affects more often ruminants, with only few reports in dogs.Case presentation: A one-year-old intact male Shih-Tzu dog was referred to Veterinary University Hospital with history of abnormal gait and generalized tonic-clonic seizures. Signs included hypermetria, abnormal nystagmus and increased myotatic reflexes. At necropsy, during the brain analysis, a cleft was observed in the left parietal and occipital lobes, creating a communication between the subarachnoid space and the left lateral ventricle, consistent with porencephaly; and also a focal atrophy of the caudal paravermal and vermal portions of the cerebellum. Furthermore, the histological examination showed cortical and cerebellar neuronal dysplasia.Conclusions: Reports of seizures due to porencephaly are rare in dogs. In this case, the dog presented a group of brain abnormalities which per se or in assemblage could result in seizure manifestation.

Polyradiculoneuropathy and neurocysticercosis: Case report

Report of a patient with the hydrocephalic and meningoencephalitic form of neurocysticercosis who simultaneously developed polyradiculoneuropathy and intracranial hypertension syndrome during the first week of treatment with albendazole. Etiologic agents associated with polyradiculoneuropathy related in the literature are cited. Some comments about the possible physiopathogeny of this entity in the presence of cysticercosis are also done. It is mentioned another case who presented polyradiculoneuropathy as the only manifestation of a probable cysticercosis of the nervous system. In this presented case, including the neurocysticercosis and even a mere coincidence of facts, some factors can have a relationship with the appearance of polyradiculoneuropathy as the surgical stress, the stress due to the severity of the clinical picture and the possible side effect of albendazole.

Organophosphate induced delayed neuropathy in genetically dissimilar chickens: Studies with tri-ortho-cresyl phosphate (TOCP) and trichlorfon

Measurements of plasma cholinesterase (pl.ChE), brain cholinesterase (Br.ChE) and brain Neuropathy Target Esterase (Br.NTE) were made in three different lineages of chickens. All birds received toxicants through gavage in a single oral dose between 08:00 and 09:00 h, after overnight fast. Babcock chickens were treated with 800 mg/kg tri-ortho-cresyl phosphate (TOCP) or 80 mg/kg trichlorfon. The TOCP group had 82% Br.NTE inhibition, when compared to the control group, and no birds displayed symptoms of clinical organophosphate-induced delayed neuropathy (OPIDN). Hy-line w36 lineage chickens were given 1600 mg/kg TOCP and despite this higher dose, Br.NTE inhibition was similar that presented by Babcock chickens. Isabrown chickens were given 1600 mg/kg TOCP or 80 mg/kg trichlorfon. At 36 h all trichlorfon treated birds had from 80 to 90% inhibition of Pl.ChE and Br.ChE, when compared to controls. However, Br.NTE was inhibited less than 20%, and there were no clinical signs of OPIDN. All TOCP treated isabrown chickens had more than 80% Br.NTE inhibition while one of them exhibited just light signs of OPIDN, two chickens became totally paralyzed. This finding suggested that chicken strain was important in the appearance of OPIDN. In addition, 70-80% of NTE inhibition was necessary but was not sufficient to produce OPIDN in chickens, since babcock and hy-line w36 chickens exhibited NTE inhibition in the range of 70-80% without clinical signs of OPIDN. © 2002 Elsevier Science Ireland Ltd. All rights reserved.

Alcohol levels in cerebrospinal fluid and blood samples from patients under pathological conditions

We measured alcohol levels by the Cordebard method in 148 CSF samples from individuals who had abstained from alcohol for at least 7 days prior to the beginning of the study. Each blood sample was accompanied by a CSF sample from the same patient. CSF samples found to be normal after analysis were used as controls. Mean alcohol concentration in blood did not differ significantly between the control group and the groups with altered CSF. The group with altered CSF had statistically higher alcohol levels in CSF than in blood. CSF lactate, glucose and protein levels were not correlated with alcohol level. The results suggest the presence of endogenous alcohol in the CSF, with levels increasing in the presence of pathological processes involving the nervous system.

Physiological and pathophysiological interactions between the respiratory central pattern generator and the sympathetic nervous system

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Cardiovascular responses produced by central injection of hydrogen peroxide in conscious rats

Reactive oxygen species (ROS) have been shown to modulate neuronal synaptic transmission and may play a role on the autonomic control of the cardiovascular system. In this study we investigated the effects produced by hydrogen peroxide (H 2O 2) injected alone or combined with the anti-oxidant agent N-acetil-l-cysteine (NAC) or catalase into the fourth brain ventricle (4th V) on mean arterial pressure and heart rate of conscious rats. Moreover the involvement of the autonomic nervous system on the cardiovascular responses to H 2O 2 into the 4th V was also investigated. Male Holtzman rats (280-320 g) with a stainless steel cannula implanted into the 4th V and polyethylene cannulas inserted into the femoral artery and vein were used. Injections of H 2O 2 (0.5, 1.0 and 1.5 μmol/0.2 μL, n = 6) into the 4th V produced transient (for 10 min) dose-dependent pressor responses. The 1.0 and 1.5 μmol doses of H 2O 2 also produced a long lasting bradycardia (at least 24 h with the high dose of H 2O 2). Prior injection of N-acetyl-l-cysteine (250 nmol/1 μL/rat) into the 4th V blockade the pressor response and attenuated the bradycardic response to H 2O 2 (1 μmol/0.5 μL/rat, n = 7) into the 4th V. Intravenous (i.v.) atropine methyl bromide (1.0 mg/kg, n = 11) abolished the bradycardia but did not affect the pressor response to H 2O 2. Prazosin hydrochloride (1.0 mg/kg, n = 6) i.v. abolished the pressor response but did not affect the bradycardia. The increase in the catalase activity (500 UEA/1 μL/rat injected into the 4th V) also abolished both, pressor and bradycardic responses to H 2O 2. The results suggest that increased ROS availability into 4th V simultaneously activate sympathetic and parasympathetic outflow inducing pressor and bradycardic responses. © 2006 Elsevier Inc. All rights reserved.

Advances in drug design based on the amino acid approach: Taurine analogues for the treatment of CNS diseases

Amino acids are well known to be an important class of compounds for the maintenance of body homeostasis and their deficit, even for the polar neuroactive aminoacids, can be controlled by supplementation. However, for the amino acid taurine (2-aminoethanesulfonic acid) this is not true. Due its special physicochemical properties, taurine is unable to cross the blood-brain barrier. In addition of injured taurine transport systems under pathological conditions, CNS supplementation of taurine is almost null. Taurine is a potent antioxidant and anti-inflammatory semi-essential amino acid extensively involved in neurological activities, acting as neurotrophic factor, binding to GABA A/glycine receptors and blocking the excitotoxicity glutamate-induced pathway leading to be a neuroprotective effect and neuromodulation. Taurine deficits have been implicated in several CNS diseases, such as Alzheimer's, Parkinson's, epilepsy and in the damage of retinal neurons. This review describes the CNS physiological functions of taurine and the development of new derivatives based on its structure useful in CNS disease treatment.&; 2012 by the authors; licensee MDPI, Basel, Switzerland.