RESUMO
Patients suffering an acute ischemic stroke can be treated with intravenous thrombolysis in the absence of contraindications. A known onset time is a prerequisite as treatment, according to guidelines, has to be started within 4.5 hours. In patients awakening with a stroke, the last time they were seen without a neurological deficit is assumed to be the time of onset. Thus, despite of lack of contraindications on initial brain imaging, these patients are largely excluded from therapy. This review discusses the underlying pathophysiological, clinical, and radiological evidence surrounding wake-up stroke and its consequences for making treatment decisions.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Sono , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/métodos , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etiologia , Humanos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Terapia Trombolítica/efeitos adversosRESUMO
OBJECTIVE: Septal area is a limbic structure that is involved in the regulation of several autonomic, learning-related and behavioral functions. Participation of this area in various physiologic functions is indicative of its extensive connections with different brain areas. It contains two major divisions: lateral septum (LS) and medial septum/diagonal band of Broca (MS/DBB). In the present work, we examined topographical distribution of projecting neurons to these divisions and quantitatively verified them. METHODS: Horseradish peroxidase (HRP) retrograde tract tracing was performed. RESULTS: Our results show that about two-thirds of projections to the septal area terminate in the LS. They mostly originate ipsilaterally from the septal area itself (8%), hippocampal formation (38%), non-specific thalamic nuclei (23%), lateral pre-optic area, lateral hypothalamus, perifornical area and mammillary complex in hypothalamus (20%), ventral tegmental area, raphe and tegmental nuclei, and also locus coeruleus in brainstem (10%). Most afferents to the MS come ipsilaterally from the septal area itself (18%), hippocampal formation (12%), lateral pre-optic area, lateral hypothalamus and mammillary complex in hypothalamus (42%), ventral tegmental area, raphe and tegmental nuclei, central gray matter and also locus coeruleus in brainstem (20%). Some afferents to the septal area originate contralaterally from the lateral hypothalamus, supramammillary area, raphe nuclei and locus coeruleus. DISCUSSION: Afferents from the interanterodorsal and mediodorsal thalamic nuclei, which increase the role of the septal area in arousal and awareness, are reported for the first time. Projecting cells to the MS support the learning-related function of this area. Projecting cells to the LS that are more scattered throughout the brain indicate its involvement in more diverse functions.
Assuntos
Mapeamento Encefálico , Tronco Encefálico/anatomia & histologia , Feixe Diagonal de Broca/anatomia & histologia , Prosencéfalo/anatomia & histologia , Prosencéfalo/fisiologia , Septo do Cérebro/anatomia & histologia , Vias Aferentes/anatomia & histologia , Vias Aferentes/fisiologia , Animais , Tronco Encefálico/fisiologia , Feixe Diagonal de Broca/fisiologia , Peroxidase do Rábano Silvestre , Imuno-Histoquímica , Masculino , Ratos , Ratos Sprague-Dawley , Septo do Cérebro/fisiologiaRESUMO
To understand the contribution of potassium (K+) channels, particularly alpha-dendrotoxin (D-type)-sensitive K+ channels (Kv.1, Kv1.2 or Kv1.6 subunits), to the generation of neuronal spike output we must have detailed information of the functional role of these channels in the neuronal membrane. Conventional intracellular recording methods in current clamp mode were used to identify the role of alpha-dendrotoxin (alpha-DTX)-sensitive K+ channel currents in shaping the spike output and modulation of neuronal properties of cerebellar Purkinje neurons (PCs) in slices. Addition of alpha-DTX revealed that D-type K+ channels play an important role in the shaping of Purkinje neuronal firing behavior. Repetitive firing capability of PCs was increased following exposure to artificial cerebrospinal fluid (aCSF) containing alpha-DTX, so that in response to the injection of 0.6 nA depolarizing current pulse of 600 ms, the number of action potentials insignificantly increased from 15 in the presence of 4-AP to 29 action potentials per second after application of DTX following pretreatment with 4-AP. These results indicate that D-type K+ channels (Kv.1, Kv1.2 or Kv1.6 subunits) may contribute to the spike frequency adaptation in PCs. Our findings suggest that the activation of voltage-dependent K+ channels (D and A types) markedly affect the firing pattern of PCs.
Assuntos
Venenos Elapídicos/farmacologia , Bloqueadores dos Canais de Potássio/farmacologia , Células de Purkinje/fisiologia , Superfamília Shaker de Canais de Potássio/fisiologia , 4-Aminopiridina/farmacologia , Potenciais de Ação/fisiologia , Animais , Eletrofisiologia , Canal de Potássio Kv1.2/efeitos dos fármacos , Canal de Potássio Kv1.2/fisiologia , Canal de Potássio Kv1.6/efeitos dos fármacos , Canal de Potássio Kv1.6/fisiologia , Masculino , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Ratos , Ratos Sprague-Dawley , Superfamília Shaker de Canais de Potássio/efeitos dos fármacosRESUMO
Under congenital thyroid hypofunction, the oro-facial large and small calcitonin gene-related peptide (CGRP) immunoreactive motoneurons were classified into strong, moderate, weak and negative intensity in offspring weaned rats. While 50% of neurons in the trigeminal motor nucleus (Mo5) were of the large type, this value dropped to 30% in hypothyroid pups. Hypothyroid trigeminal accessory nucleus (Mo5-AC) contained 10% large motoneurons versus about 45% in normal pups. Normal facial nucleus (Mo7) had 20% large motoneurons in contrast with 10% in hypothyroid pups. These values are significant in comparison with the normal pattern of oro-facial CGRP positive immunoreactive motoneurons as well as those devoid of immunostaining.
Assuntos
Peptídeo Relacionado com Gene de Calcitonina/fisiologia , Hipotireoidismo Congênito , Hipotireoidismo/fisiopatologia , Neurônios Motores/fisiologia , Glândula Tireoide/fisiopatologia , Animais , Peso Corporal , Face/inervação , Feminino , Imuno-Histoquímica , Neurônios Motores/classificação , Neurônios Motores/ultraestrutura , Gravidez , Ratos , Ratos Sprague-Dawley , Glândula Tireoide/ultraestruturaRESUMO
Afferents to the median-paramedian raphe nuclear complex, which contains the B8 serotonergic cell group, were investigated in the rat with neuroanatomical and transmitter-selective retrograde labelling techniques. Injection of sensitive retrograde tracers, cholera toxin genoid or wheat germ agglutinin conjugated horseradish peroxidase into the median raphe resulted in labelling of neurons in a large number of brain regions. Projections from 26 of these regions are supported by available orthograde tracing data; the cingulate cortex, bed nucleus of stria terminalis, medial septum and diagonal band of Broca, ventral pallidum, medial and lateral preoptic areas, lateral hypothalamus, dorsomedial nucleus of hypothalamus, lateral habenula, interpeduncular nucleus, substantia nigra, central (periaqueductal) gray, and laterodorsal tegmental nucleus seem to represent major sources of afferents to the median-paramedian raphe complex. Retrogradely labelled cells were also observed in a number of regions for which anterograde tracing data are not available, including the perifornical hypothalamic nucleus, ventral premammillary nucleus, supramammillary and submammillothalamic nuclei and the B9 area. Possible excitatory amino acid afferents were identified with retrograde D-[3H]aspartate labelling. Microinjection of D-[3H]aspartate at a low concentration, 10(-4) M in 50 nl, resulted in retrograde labelling of a limited number of median raphe afferents. The most prominent labelling was observed in the lateral habenula and the interpeduncular nucleus, but retrogradely labelled cells were also noted in the medial and lateral preoptic areas, lateral and dorsal hypothalamus, ventral tegmental area, laterodorsal tegmental nucleus, medial parabrachial nucleus, and the pontine tegmentum. After injections of 10(-3) M D-[3H]aspartate selective labelling also appeared in more distant afferent regions, including cells in cingulate cortex, and in some regions located at shorter distances, such as the supramammillary nucleus. Injections of D-[3H]aspartate at high concentration, 10(-2) M, resulted in the appearance of weakly to moderately labelled cells in most afferent areas which were devoid of labelled cells after injections of lower concentrations, suggesting that this labelling may be non-specific. It was concluded that the median-paramedian raphe receives afferents from a large number of forebrain and hypothalamic regions, while relatively few brain stem regions project to this nuclear complex. The selectivity of retrograde labelling with D-[3H]aspartate was found to be concentration dependent, and it is suggested that the connections showing high affinity for D-[3H]aspartate may use excitatory amino acids as transmitters. Excitatory amino acid inputs from lateral habenula and interpeduncular nucleus may play predominant roles in the control of ascending serotonergic and non-serotonergic projections originating in the median and paramedian raphe nuclei.
Assuntos
Aminoácidos/metabolismo , Ácido Aspártico/metabolismo , Toxina da Cólera , Neurônios Aferentes/fisiologia , Núcleos da Rafe/fisiologia , Aglutininas do Germe de Trigo , Animais , Encéfalo/anatomia & histologia , Feminino , Peroxidase do Rábano Silvestre , Imuno-Histoquímica , Núcleos da Rafe/anatomia & histologia , Núcleos da Rafe/citologia , Ratos , Ratos Endogâmicos , Serotonina/fisiologia , Técnicas EstereotáxicasRESUMO
Anterograde tracing from dorsal raphe neurons by Phaseolus vulgaris leucoagglutinin and serotonin immunocytochemistry revealed no serotonergic projections from raphe nuclei to cerebral pial vessels in the rat. However, cerebrovascular nerve fibres, mainly located in major pial arteries, were immunoreactive to tryptophan-5-hydroxylase antibodies as previously shown by others. It thus seems that the rate-limiting enzyme catalysing the biosynthesis of serotonin, tryptophan-5-hydroxylase, is present in cerebrovascular nerve fibres which do not originate in the dorsal raphe nucleus and which do not contain enough serotonin to be labelled by serotonin immunocytochemistry. We also observed tryptophan hydroxylase-immunoreactive but no serotonin-immunoreactive nerve fibres in the femoral artery and, occasionally, in the dura mater. The femoral artery, like the dura mater, contained numerous mast cells reacting positively to both tryptophan hydroxylase and to serotonin immunocytochemistry. The colocalization of the enzyme and its final product thus appears to be a general feature, since it has already been demonstrated within the central nervous system. The only exception appears to be the tryptophan hydroxylase-immunoreactive nerves present in cerebral and peripheral vessels. These results suggest that there is not a true serotonergic (i.e. serotonin-containing) innervation in cerebral blood vessels. They also strongly suggest that the cerebrovascular nerve fibres which appear to contain tryptophan hydroxylase do not originate in the raphe nuclei.
Assuntos
Circulação Cerebrovascular , Dura-Máter/fisiologia , Pia-Máter/fisiologia , Núcleos da Rafe/fisiologia , Serotonina/análise , Triptofano Hidroxilase/análise , Animais , Transporte Axonal , Dura-Máter/irrigação sanguínea , Dura-Máter/citologia , Feminino , Artéria Femoral/citologia , Artéria Femoral/enzimologia , Imuno-Histoquímica , Masculino , Meninges/citologia , Meninges/enzimologia , Fibras Nervosas/enzimologia , Fibras Nervosas/ultraestrutura , Fito-Hemaglutininas , Pia-Máter/irrigação sanguínea , Pia-Máter/citologia , Núcleos da Rafe/irrigação sanguínea , Núcleos da Rafe/citologia , Ratos , Ratos Endogâmicos , Ratos WistarRESUMO
There is strong evidence that oxidative stress participates in the etiology of Parkinson's disease (PD). We designed this study to investigate the neuroprotective effect of vitamin E in the early model of PD. For this purpose, unilateral intrastriatal 6-hydroxydopamine (12.5 microg/5 microl) lesioned rats were pretreated intramuscularly with D-alpha-tocopheryl acid succinate (24 I.U./kg, i.m.) 1 h before and three times per week for 1 month post-surgery. Apomorphine- and amphetamine-induced rotational behavior was measured postlesion fortnightly. A parallel tyrosine hydroxylase immunoreactivity and wheat germ agglutinin-horse radish peroxidase (WGA-HRP) tract-tracing study was performed to evaluate the vitamin E pretreatment efficacy. Tyrosine hydroxylase-immunohistochemical analyses showed a reduction of 18% in ipsilateral substantia nigra pars compacta (SNC) cell number of the vitamin E-pretreated lesioned (L+E) group comparing with contralateral side. The cell number dropped to 53% in the lesioned (L+V) group. In addition, retrograde-labeled neurons in ipsilateral SNC were reduced by up to 30% in the L+E group and 65% in the L+V group. Behavioral tests revealed that there are 74% and 68% reductions in contraversive and ipsiversive rotations in the L+E group, respectively, as compared with the L+V group. Therefore repeated intramuscular administration of vitamin E exerts a rapid protective effect on the nigrostriatal dopaminergic neurons in the early unilateral model of PD.
Assuntos
Fármacos Neuroprotetores/uso terapêutico , Transtornos Parkinsonianos/tratamento farmacológico , Vitamina E/uso terapêutico , Anfetamina/farmacologia , Animais , Apomorfina/farmacologia , Atrofia , Transporte Axonal , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/patologia , Modelos Animais de Doenças , Masculino , Atividade Motora/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/patologia , Oxidopamina , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/fisiopatologia , Ratos , Ratos Sprague-Dawley , Rotação , Substância Negra/efeitos dos fármacos , Substância Negra/patologia , Fatores de Tempo , Tirosina 3-Mono-Oxigenase/análise , Conjugado Aglutinina do Germe de Trigo-Peroxidase do Rábano SilvestreRESUMO
Involvement of median raphe nucleus (MRN) in acquisition, consolidation and retrieval of passive avoidance (PA) was investigated with functional suppression of this area by lidocaine. Rats carrying a chronically implanted cannula aimed at the MRN were trained on a step-through passive avoidance task and received intra-MRN injection of lidocaine or saline 5 min before training or 5, 90 and 360 min after acquisition trial or 5 min before the retrieval test. Lidocaine MRN inactivation had no effect on PA learning. Lidocaine injected 5 and 90 min after the acquisition trial significantly enhanced avoidance of the dark compartment in comparison with the control group injected with saline. But PA retention was not affected by lidocaine injected 360 min after acquisition or 5 min before training. Retention latency significantly increased, when lidocaine injected 5 min before retrieval test. Step-through latency of naive rats was not affected by MRN blockade. Furthermore, reversible inactivation of MRN did not have a significant effect on locomotor activity. Our results indicate that the MRN contributes to PA consolidation at least until 90 min after acquisition and involves in PA retrieval. It is concluded that functional ablation of the MRN may disrupt the inhibitory actions of MRN projections to sub-cortical circuits participating in PA memorization and retrieval.
Assuntos
Aprendizagem da Esquiva/fisiologia , Aprendizagem/fisiologia , Rememoração Mental/fisiologia , Núcleos da Rafe/fisiologia , Análise de Variância , Anestésicos Locais , Animais , Lidocaína/farmacologia , Masculino , Microinjeções , Atividade Motora/fisiologia , RatosRESUMO
We assessed the effects of reversible inactivation of the medial septal area (MSA) on long-term potentiation (LTP) and recurrent inhibition in the dentate gyrus of urethane-anesthetized rats, in vivo. The septal input to the hippocampus was temporarily eliminated by injection of tetrodotoxin (TTX, 10 ng/l microliter) into the MSA. In Experiment 1, LTP inducibility was examined in the perforant-dentate gyrus synapses in the MSA inactivated and control rats by 2 high-frequency stimulation (HFS), 5 min apart, applied to the perforant pathway (PP). The magnitude of potentiation was evaluated as the percentage change in the population spike (PS) amplitude at 5, 30, 60 or 120 min after the second HFS. The PS amplitude in the MSA inactivated rats was significantly lower than those of control group at 120 but not 5, 30 or 60 min after the second HFS. The MSA inactivation itself had no effect on the basal responses evoked by test stimuli. In Experiment 2, the MSA inactivation did not affect the efficacy of recurrent inhibition in the perforant-dentate gyrus synapses produced by paired pulses applied to the PP at 10- and 20-ms interpulse intervals. These results indicate that: (1) although hippocampal synapses can be still potentiated after the HFS in the MSA inactivated animals, a faster decay of LTP may be due to elimination of the MSA output amplification on synaptic responses mediated by excitatory amino acids; and (2) the recurrent inhibition mechanism in the dentate gyrus of the hippocampus is not probably affected by the MSA inactivation.
Assuntos
Hipocampo/fisiologia , Potenciação de Longa Duração , Inibição Neural , Septo Pelúcido/fisiologia , Potenciais de Ação , Animais , Potenciação de Longa Duração/efeitos dos fármacos , Masculino , Ratos , Tetrodotoxina/farmacologiaRESUMO
Selective retrograde labelling was used as an autoradiographic method to identify possible excitatory amino acid afferents to nucleus raphe magnus (NRM). Injections of 25-50 nl 10(-2) or 10(-3) M D-[3H]aspartate into the NRM resulted in prominent labelling of cells in ventrolateral mesencephalic periaqueductal gray (PAG). Electrophysiologically, stimulation in ventrolateral PAG excited cells in NRM with a latency of 2-12 ms. With many cells, microelectrophoretic application of the excitatory amino acid antagonists, kynurenate and gamma-D-glutamyl-glycine, resulted in a reversible reduction of the PAG-evoked response. Selective antagonists of N-methyl-D-aspartate (NMDA) were less effective. It is suggested that neurones in the ventrolateral PAG projecting to NRM utilize an excitatory amino acid or structurally related compound as a transmitter, and that this transmitter acts on receptors of the non-NMDA type.
Assuntos
Aminoácidos/fisiologia , Substância Cinzenta Periaquedutal/fisiologia , Núcleos da Rafe/fisiologia , Transmissão Sináptica , Animais , Autorradiografia , Eletrofisiologia , Fibras Nervosas/fisiologia , Neurotransmissores/fisiologia , Ratos , Ratos EndogâmicosRESUMO
Alterations in the intrinsic properties of Purkinje cells (PCs) may contribute to the abnormal motor performance observed in ataxic rats. To investigate whether such changes in the intrinsic neuronal excitability could be attributed to the role of Ca(2+)-activated K(+) channels (K(Ca)), whole cell current clamp recordings were made from PCs in cerebellar slices of control and ataxic rats. 3-AP induced profound alterations in the intrinsic properties of PCs, as evidenced by a significant increase in both the membrane input resistance and the initial discharge frequency, along with the disruption of the firing regularity. In control PCs, the blockade of small conductance K(Ca) channels by UCL1684 resulted in a significant increase in the membrane input resistance, action potential (AP) half-width, time to peak of the AP and initial discharge frequency. SK channel blockade also significantly decreased the neuronal discharge regularity, the peak amplitude of the AP, the amplitude of the afterhyperpolarization and the spike frequency adaptation ratio. In contrast, in ataxic rats, both the firing regularity and the initial firing frequency were significantly increased by the blockade of SK channels. In conclusion, ataxia may arise from alterations in the functional contribution of SK channels, to the intrinsic properties of PCs.