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1.
Transfusion ; 59(S2): 1529-1538, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30980755

RESUMO

Traumatic brain injury (TBI) is a common disorder with high morbidity and mortality, accounting for one in every three deaths due to injury. Older adults are especially vulnerable. They have the highest rates of TBI-related hospitalization and death. There are about 2.5 to 6.5 million US citizens living with TBI-related disabilities. The cost of care is very high. Aside from prevention, little can be done for the initial primary injury of neurotrauma. The tissue damage incurred directly from the inciting event, for example, a blow to the head or bullet penetration, is largely complete by the time medical care can be instituted. However, this event will give rise to secondary injury, which consists of a cascade of changes on a cellular and molecular level, including cellular swelling, loss of membrane gradients, influx of immune and inflammatory mediators, excitotoxic transmitter release, and changes in calcium dynamics. Clinicians can intercede with interventions to improve outcome in the mitigating secondary injury. The fundamental concepts in critical care management of moderate and severe TBI focus on alleviating intracranial pressure and avoiding hypotension and hypoxia. In addition to these important considerations, mechanical ventilation, appropriate transfusion of blood products, management of paroxysmal sympathetic hyperactivity, using nutrition as a therapy, and, of course, venous thromboembolism and seizure prevention are all essential in the management of moderate to severe TBI patients. These concepts will be reviewed using the recent 2016 Brain Trauma Foundation Guidelines to discuss best practices and identify future research priorities.


Assuntos
Transfusão de Componentes Sanguíneos , Lesões Encefálicas Traumáticas , Cuidados Críticos/métodos , Hospitalização , Adulto , Idoso , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/mortalidade , Lesões Encefálicas Traumáticas/fisiopatologia , Lesões Encefálicas Traumáticas/terapia , Feminino , Humanos , Hipotensão/etiologia , Hipotensão/mortalidade , Hipotensão/fisiopatologia , Hipotensão/prevenção & controle , Hipóxia Encefálica/etiologia , Hipóxia Encefálica/mortalidade , Hipóxia Encefálica/fisiopatologia , Hipóxia Encefálica/prevenção & controle , Hipertensão Intracraniana/etiologia , Hipertensão Intracraniana/mortalidade , Hipertensão Intracraniana/fisiopatologia , Hipertensão Intracraniana/prevenção & controle , Masculino , Pessoa de Meia-Idade , Convulsões/etiologia , Convulsões/mortalidade , Convulsões/fisiopatologia , Convulsões/prevenção & controle , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/mortalidade , Tromboembolia Venosa/fisiopatologia , Tromboembolia Venosa/prevenção & controle
2.
Semin Respir Crit Care Med ; 38(6): 745-759, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29262432

RESUMO

Spontaneous intracerebral hemorrhage (ICH) is the most common cause of intraventricular hemorrhage (IVH) in adults. Complicating approximately 40% of ICH cases, IVH adds to the morbidity and mortality of this often fatal form of stroke. It is also a severity factor that complicates subarachnoid hemorrhage and traumatic brain injury, along with other less common causes of intracranial bleeding. Medical and surgical interventions to date have focused on limiting ICH and IVH expansion, controlling intracranial pressure, and relieving obstructive hydrocephalus. The placement of an external ventricular drain (EVD) can achieve the latter two goals but has not demonstrated improvement in clinical outcomes beyond mortality reduction. More recently, intraventricular fibrinolysis, utilizing the EVD, has gained interest as a safe and potentially effective method to maintain catheter patency and facilitate hematoma removal. A recent phase III clinical trial evaluating the efficacy of intraventricular alteplase versus intraventricular saline showed a mortality benefit, but failed to meet the primary endpoint of significant functional improvement. However, planned subgroup analysis focusing on patients with IVH volume > 20 mL, and those with IVH removal > 85% suggest that significant functional benefits may be attainable with this therapy. The practice of intraventricular fibrinolysis for spontaneous IVH is not the standard of care; however, based on 20 years of experience, it meets thresholds as a safe intervention, and in those patients with a high burden of intraventricular blood, aggressive clearance may lead to improved quality of life in survivors of this morbid syndrome.


Assuntos
Hemorragia Cerebral/tratamento farmacológico , Fibrinolíticos/administração & dosagem , Ativador de Plasminogênio Tecidual/administração & dosagem , Adulto , Hemorragia Cerebral/mortalidade , Hemorragia Cerebral/fisiopatologia , Drenagem/métodos , Fibrinolíticos/efeitos adversos , Humanos , Injeções Intraventriculares , Qualidade de Vida , Índice de Gravidade de Doença , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/fisiopatologia , Ativador de Plasminogênio Tecidual/efeitos adversos
3.
Can J Neurol Sci ; 44(3): 295-303, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28091345

RESUMO

BACKGROUND: Critical illness polyneuropathy (CIN) and critical illness myopathy (CIM), together "ICU-Acquired weakness (ICUAW)," occur frequently in septic patients. One of the proposed mechanisms for ICUAW includes prolonged inactivation of sodium channels. Propofol, used commonly in patients with acute respiratory failure (ARF), primarily acts via enhancement of GABAergic transmission but may also increase sodium channel inactivation, suggesting a potential interaction. METHODS: Electronic medical records and EMG reports of patients with ICUAW and a diagnosis of either sepsis, septicaemia, severe sepsis, or septic shock, concurrent with a diagnosis of acute respiratory failure (ARF), were retrospectively analyzed in a single center university hospital. RESULTS: 74 cases were identified (50.0% men, age 58±14 years), and compared to age- and sex-matched controls. Of these, 51 (69%) had CIN, 19 (26%) had CIM, and 4 (5%) had both. Propofol exposure was significantly higher in patients with ICUAW compared to controls (63.5% vs. 33.8%, p<0.001). The odds ratio of developing ICUAW with propofol exposure was 3.4 (95% CI:1.7-6.7, p<0.001). Patients with ICUAW had significantly more days in hospital (59±44 vs. 30±23) and ICU (38±26 vs. 17±13), days dependent on mechanical ventilation (27±21 vs. 13±16), and rates of tracheostomy (79.7% vs. 36.5%) and gastrostomy (75.7% vs. 25.7%) (all p<0.001). They also received a significantly higher number of distinct intravenous antibiotics, cumulative days of antibiotic therapy, and exposure to vasopressors and paralytics. CONCLUSIONS: Propofol exposure may increase the risk of ICUAW in septic patients. An interaction through sodium channel inactivation is hypothesized.


Assuntos
Unidades de Terapia Intensiva/tendências , Debilidade Muscular/induzido quimicamente , Debilidade Muscular/epidemiologia , Propofol/efeitos adversos , Síndrome do Desconforto Respiratório/epidemiologia , Sepse/epidemiologia , Adulto , Idoso , Estudos de Coortes , Estado Terminal/epidemiologia , Estado Terminal/terapia , Registros Eletrônicos de Saúde/tendências , Feminino , Humanos , Hipnóticos e Sedativos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Síndrome do Desconforto Respiratório/terapia , Fatores de Risco , Sepse/terapia , Canais de Sódio/fisiologia
4.
Neurocrit Care ; 27(2): 276-286, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28004327

RESUMO

The brain, due to intensive cellular processes and maintenance of electrochemical gradients, is heavily dependent on a constant supply of energy. Brain injury, and critical illness in general, induces a state of increased metabolism and catabolism, which has been proven to lead to poor outcomes. Of all the biochemical interventions undertaken in the ICU, providing nutritional support is perhaps one of the most undervalued, but potentially among the safest, and most effective interventions. Adequate provisions of calories and protein have been shown to improve patient outcomes, and guidelines for the nutritional support of the critically ill patient are reviewed. However, there are no such specific guidelines for the critically ill patient with neurological injury. Patients with primary or secondary neurological disorders are frequently undernourished, while data suggest this population would benefit from early and adequate nutritional support, although comprehensive clinical evidence is lacking. We review the joint recommendations from the Society for Critical Care Medicine and the American Society for Parenteral and Enteral Nutrition, as they pertain to neurocritical care, and assess the recommendations for addressing nutrition in this patient population.


Assuntos
Encéfalo/metabolismo , Cuidados Críticos/normas , Terapia Nutricional/normas , Guias de Prática Clínica como Assunto/normas , Traumatismos do Sistema Nervoso/metabolismo , Traumatismos do Sistema Nervoso/terapia , Humanos
5.
Neurocrit Care ; 24(3): 361-70, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26293923

RESUMO

BACKGROUND: Approximately one-third of patients with isolated traumatic brain injury (iTBI) present with acute traumatic coagulopathy (ATC). ATC is associated with increased morbidity and mortality. Its effects on long-term functional and cognitive outcomes are not as well characterized. METHODS: Data from the Citicoline Brain Injury Treatment Trial (COBRIT) were analyzed retrospectively. Exclusion criteria were renal failure or malignancy, and any extracranial injury severity score >3. ATC was defined as INR > 1.3, PTT > 38 s, or platelets < 100 K, determined at baseline, and during the first 7 days of hospitalization. RESULTS: Six hundred forty-seven patients were included; 21 % were found to have ATC. Highest incidence occurred at baseline, and Day Two. Forty-two percent of ATC patients had a GCS < 8, compared with 11.3 % of non-ATC patients (p < 0.001). A significantly higher proportion of ATC patients was transfused blood products, required greater than 4L of fluids, demonstrated hyperthermia and hypothermia, were hypotensive and demonstrated elevated lactate when compared to non-ATC patients. In-hospital mortality, mean hospital length of stay, incidence of DVT and seizures were also significantly higher in ATC patients. A significantly lower portion of ATC patients had good outcomes on the GOS-E (i.e., score > 6), and the DRS (i.e., score < 2) at 180 days, for which ATC was found to be an independent predictor with binary logistic regression. ATC patients also performed significantly worse on several components of the CVLT-II at 180 days. CONCLUSIONS: ATC accompanying iTBI is associated with worse functional and cognitive outcomes at 180 days.


Assuntos
Transtornos da Coagulação Sanguínea/fisiopatologia , Lesões Encefálicas Traumáticas/fisiopatologia , Mortalidade Hospitalar , Escala de Gravidade do Ferimento , Tempo de Internação/estatística & dados numéricos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Adulto , Transtornos da Coagulação Sanguínea/epidemiologia , Transtornos da Coagulação Sanguínea/etiologia , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/epidemiologia , Citidina Difosfato Colina/uso terapêutico , Feminino , Seguimentos , Escala de Coma de Glasgow , Escala de Resultado de Glasgow , Humanos , Masculino , Pessoa de Meia-Idade , Nootrópicos/uso terapêutico , Estudos Retrospectivos , Adulto Jovem
6.
Can J Neurol Sci ; 39(3): 323-7, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22547512

RESUMO

OBJECTIVE: To explore the use of magnesium (Mg), an endogenous ion and enzymatic co-factor used in a variety of medical applications, for the treatment of epileptic seizures resistant to traditional medical therapy. BACKGROUND: For almost a century, Mg has been used as prophylaxis and treatment of seizures associated with eclampsia. Mg is a CNS depressant, with numerous functions intracellularly and extracellularly. However, because of the availability of well studied anticonvulsant drugs, Mg has not been tested widely in the treatment of epileptic seizures. METHODS: A retrospective chart review of 22 cases of drug resistant epilepsy, where a trial of empiric oral Mg supplementation (mainly in the form of Mg-oxide) was conducted. RESULTS: Oral Mg supplementation was associated with a significant decrease in the number of seizure days per month, from 15.3 ± 13.2 (mean ± SD) to 10.2 ± 12.6 at first follow up (3-6 months, p=0.021), and to 7.8 ± 10.0 seizure days/month at second follow up (6-12 months, p=0.004). Thirty-six percent had a response rate of 75% or greater at second follow-up. Two patients reported seizure freedom. Most patients were well maintained on MgO 420 mg twice a day, or in 2 cases, Mg Lactate, without significant adverse effects, the most frequent being diarrhea (4/22). DISCUSSION: These results suggest that oral Mg supplementation may prove to be a worthwhile adjunctive medication in treating drug intractable epilepsy. CONCLUSIONS: A prospective, double-blinded, placebo controlled study is warranted to evaluate the potential of Mg for the treatment of drug-resistant seizures.


Assuntos
Anticonvulsivantes/administração & dosagem , Magnésio/administração & dosagem , Convulsões/tratamento farmacológico , Administração Oral , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
7.
J Crit Care ; 44: 323-330, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29268200

RESUMO

PURPOSE: Genetic deletions decreasing serum alpha-Klotho (alpha-KL) have been associated with rapid aging, multi-organ failure and increased mortality in experimental sepsis. We hypothesized that lower alpha-KL obtained at the onset of septic shock correlates with higher mortality. MATERIALS AND METHODS: Prospective cohort of 104 adult patients with septic shock. Alpha-KL was measured via ELISA on serum collected on the day of enrollment (within 72h from the onset of shock). Relationship between alpha-KL and clinical outcome measures was evaluated in uni- and multi-variable models. RESULTS: Median (IQR) alpha-KL was 816 (1020.4) pg/mL and demonstrated a bimodal distribution with two distinct populations, Cohort A [n=97, median alpha-KL 789.3 (767.1)] and Cohort B [n=7, median alpha-KL 4365.1(1374.4), >1.5 IQR greater than Cohort A]. Within Cohort A, ICU non-survivors had significantly higher serum alpha-KL compared to survivors as well as significantly higher APACHE II and SOFA scores, rates of mechanical ventilation, and serum BUN, creatinine, calcium, phosphorus and lactate (all p≤0.05). Serum alpha-KL≥1005, the highest tertile, was an independent predictor of ICU mortality when controlling for co-variates (p=0.028, 95% CI 1.143-11.136). CONCLUSIONS: Elevated serum alpha-KL in patients with septic shock is independently associated with higher mortality. Further studies are needed to corroborate these findings.


Assuntos
Glucuronidase/sangue , Choque Séptico/sangue , Estresse Fisiológico/fisiologia , Idoso , Biomarcadores/sangue , Feminino , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Proteínas Klotho , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Choque Séptico/mortalidade
8.
Case Rep Neurol Med ; 2015: 673724, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26770849

RESUMO

Objective. Stroke is a clinical diagnosis, with a history and physical examination significant for acute onset focal neurological symptoms and signs, often occurring in patients with known vascular risk factors and is frequently confirmed radiographically. Case Report. A 79-year-old right-handed woman, with a past medical history of hypertension, hyperlipidemia, and prior transient ischemic attack (TIA), presented with acute onset global aphasia and right hemiparesis, in the absence of fever or prodrome. This was initially diagnosed as a proximal left middle cerebral artery (MCA) stroke. However, CT perfusion failed to show evidence of reduced blood volume, and CT angiogram did not show evidence of a proximal vessel occlusion. Furthermore, MRI brain did not demonstrate any areas of restricted diffusion. EEG demonstrated left temporal periodic lateralized epileptiform discharges (PLEDs). The patient was empirically loaded with a bolus valproic acid and started on acyclovir, both intravenously. CSF examination demonstrated a pleocytosis and PCR confirmed the diagnosis of herpes simplex viral encephalitis (HSVE). Conclusions. HSVE classically presents in a nonspecific fashion with fever, headache, and altered mental status. However, acute focal neurological signs, mimicking stroke, are possible. A high degree of suspicion is required to institute appropriate therapy and decrease morbidity and mortality associated with HSVE.

9.
Case Rep Neurol Med ; 2015: 601706, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26180647

RESUMO

Objectives. Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disorder that is often preceded by infection or recent vaccination. Encephalopathy and focal neurological deficits are usually manifest several weeks after a prodromal illness with rapidly progressive neurologic decline. ADEM is most commonly seen in children and young adults, in which prognosis is favorable, but very few cases have been reported of older adults with ADEM and thus their clinical course is unknown. Methods. Here we present a case of ADEM in a middle-aged adult that recovered well after treatment. Results. A 62-year-old man presented with encephalopathy and rapid neurological decline following a gastrointestinal illness. A brain MRI revealed extensive supratentorial white matter hyperintensities consistent with ADEM and thus he was started on high dose intravenous methylprednisolone. He underwent a brain biopsy showing widespread white matter inflammation secondary to demyelination. At discharge, his neurological exam had significantly improved with continued steroid treatment and four months later, he was able to perform his ADLs. Conclusions. This case of ADEM in a middle-aged adult represents an excellent response to high dose steroid treatment with a remarkable neurological recovery. Thus it behooves one to treat suspected cases of ADEM in an adult patient aggressively, as outcome can be favorable.

11.
Epilepsy Res ; 83(2-3): 243-8, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19136235

RESUMO

BACKGROUND: The neuropathology of hypoglycemia and its mechanisms have been well studied. However, the physiopathogenesis of hypoglycemia-related seizures has escaped elucidation. Various animal models reportedly show "seizures" when rendered hypoglycemic, however, correlation with the electroencephalogram (EEG) is inconsistent. In order to characterize the role of the hippocampus and frontal neocortex in the generation of hypoglycemic seizures, this study was undertaken. METHODS: Adult rats were implanted stereotaxically with electrodes in the left hippocampus and right frontal cortex. After 1 week, they were fasted 18-24h, then injected intraperitoneally with insulin, 35 IU/kg. Simultaneous EEG/video monitoring was conducted. RESULTS: Interpretable EEG recordings were obtained in 8/12 animals. Two showed poor association of seizure-like behaviour (neck extension, vocalizations, tonic extension of the tail, digging or running limb movements) with ictal EEG patterns. Four animals exhibited such behaviours during periods of high amplitude polymorphic slow wave activity, burst-suppression patterns or non-rhythmic spiking. Two others were encephalopathic (behaviourally and electroencephalographically) until death. CONCLUSIONS: Not all animals develop seizure-like behaviour when hypoglycemic. If these are seizures, they may originate from subcortical structures, or the "convulsive" behaviours observed may simply be flight/fight reflexes released during profound encephalopathy. Spike activity in the EEG may be a manifestation of this state. Recording EEG from rat cortex and hippocampus during seizure-like activity brought on by hypoglycemia correlates poorly with seizure-like behaviours suggesting that the relevant electrophysiological correlates, if present, are generated from deeper brain structures.


Assuntos
Eletroencefalografia , Hipoglicemia/complicações , Convulsões/etiologia , Vigília/fisiologia , Animais , Comportamento Animal , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Modelos Animais de Doenças , Eletrodos Implantados , Privação de Alimentos , Hipoglicemia/etiologia , Insulina , Masculino , Ratos , Ratos Sprague-Dawley
12.
Neurobiol Dis ; 29(2): 201-9, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17919917

RESUMO

The brain is heavily dependant on glucose for its function and survival. Hypoglycemia can have severe, irreversible consequences, including seizures, coma and death. However, the in vivo content of brain glycogen, the storage form of glucose, is meager and is a function of both neuronal activity and glucose concentration. In the intact in vitro hippocampus isolated from mice aged postnatal days 8-13, we have recently characterized a novel model of hypoglycemic seizures, wherein seizures were abolished by various neuroprotective strategies. We had hypothesized that these strategies might act, in part, by increasing cerebral glycogen content. In the present experiments, it was found that neither decreasing temperature nor increasing glucose concentrations (above 2 mM) significantly increased hippocampal glycogen content. Preparations of isolated frontal neocortex in vitro do not produce hypoglycemic seizures yet it was found they contained significantly lower glycogen content as compared to the isolated intact hippocampus. Further, the application of either TTX, or a cocktail containing APV, CNQX and gabazine, to block synaptic activity, did not increase, but paradoxically decreased, hippocampal glycogen content in the isolated intact hippocampus. Significant decreases in glycogen were noted when neuronal activity was increased via incubation with l-aspartate (500 muM) or low Mg(2+). Lastly, we examined the incidence of hypoglycemic seizures in hippocampi isolated from mice aged 15-19 and 22-24 days, and compared it to the incidence of hypoglycemic seizures of hippocampi isolated from mice aged 8-13 days described previously (Abdelmalik et al., 2007 Neurobiol Dis 26(3):646-660). It was noted that hypoglycemic seizures were generated less frequently, and had less impact on synaptic transmission in hippocmpi from PD 22-24 as compared to hippocampi from mice PD 15-19 or PD 8-13. However, hippocampi from 8- to 13-day-old mice had significantly more glycogen than the other two age groups. The present data suggest that none of the interventions which abolish hypoglycemic seizures increases glycogen content, and that low glycogen content, per se, may not predispose to the generation of hypoglycemic seizures.


Assuntos
Cerebelo/metabolismo , Glicogênio/metabolismo , Hipocampo/metabolismo , Convulsões/metabolismo , Fatores Etários , Análise de Variância , Anestésicos Locais/administração & dosagem , Animais , Animais Recém-Nascidos , Ácido Aspártico/farmacologia , Modelos Animais de Doenças , Combinação de Medicamentos , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Glucose/administração & dosagem , Hipocampo/efeitos dos fármacos , Hipoglicemia/complicações , Hipoglicemia/patologia , Técnicas In Vitro , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Convulsões/tratamento farmacológico , Convulsões/patologia , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/fisiologia , Transmissão Sináptica/efeitos da radiação , Tetrodotoxina/administração & dosagem
13.
Neurobiol Dis ; 26(3): 646-60, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17459717

RESUMO

Severe hypoglycemia constitutes a medical emergency, involving seizures, coma and death. We hypothesized that seizures, during limited substrate availability, aggravate hypoglycemia-induced brain damage. Using immature isolated, intact hippocampi and frontal neocortical blocks subjected to low glucose perfusion, we characterized hypoglycemic (neuroglycopenic) seizures in vitro during transient hypoglycemia and their effects on synaptic transmission and glycogen content. Hippocampal hypoglycemic seizures were always followed by an irreversible reduction (>60% loss) in synaptic transmission and were occasionally accompanied by spreading depression-like events. Hypoglycemic seizures occurred more frequently with decreasing "hypoglycemic" extracellular glucose concentrations. In contrast, no hypoglycemic seizures were generated in the neocortex during transient hypoglycemia, and the reduction of synaptic transmission was reversible (<60% loss). Hypoglycemic seizures in the hippocampus were abolished by NMDA and non-NMDA antagonists. The anticonvulsant, midazolam, but neither phenytoin nor valproate, also abolished hypoglycemic seizures. Non-glycolytic, oxidative substrates attenuated, but did not abolish, hypoglycemic seizure activity and were unable to support synaptic transmission, even in the presence of the adenosine (A1) antagonist, DPCPX. Complete prevention of hypoglycemic seizures always led to the maintenance of synaptic transmission. A quantitative glycogen assay demonstrated that hypoglycemic seizures, in vitro, during hypoglycemia deplete hippocampal glycogen. These data suggest that suppressing seizures during hypoglycemia may decrease subsequent neuronal damage and dysfunction.


Assuntos
Hipocampo/metabolismo , Hipoglicemia/complicações , Degeneração Neural/metabolismo , Neurônios/metabolismo , Convulsões/etiologia , Convulsões/metabolismo , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Antagonistas do Receptor A1 de Adenosina , Animais , Anticonvulsivantes/farmacologia , Depressão Alastrante da Atividade Elétrica Cortical/efeitos dos fármacos , Depressão Alastrante da Atividade Elétrica Cortical/fisiologia , Modelos Animais de Doenças , Antagonistas de Aminoácidos Excitatórios/farmacologia , Glucose/metabolismo , Glicogênio/análise , Glicogênio/metabolismo , Hipocampo/fisiopatologia , Hipoglicemia/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Midazolam/farmacologia , Degeneração Neural/etiologia , Degeneração Neural/fisiopatologia , Neurônios/efeitos dos fármacos , Receptor A1 de Adenosina/metabolismo , Convulsões/fisiopatologia , Transmissão Sináptica/fisiologia
14.
Epilepsia ; 46(3): 356-66, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15730532

RESUMO

PURPOSE: The temporal lobe seems particularly susceptible to seizure activity. Mesial temporal lobe structures, including the hippocampus, have the lowest seizure thresholds in the brain. Conversely, thresholds in the frontal neocortex are significantly higher. The development of intact, isolated preparations of hippocampus and neocortex in vitro allows for study into mechanisms governing seizure threshold. METHODS: Epileptiform discharges in isolated mouse neocortical blocks were compared with the contralateral intact hippocampus, isolated from the same brain, by using the low-Mg2+, 4 aminopyridine (4-AP), and low-Ca2+ in vitro seizure models. The pharmacology of low Mg(2+)-induced ictal-like events (ILEs) generated in the hippocampus and neocortex was then compared by using glutamatergic antagonists DL-2-amino-5-phosphonovaleric acid (APV) and 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX), and the Ca2+ channel antagonist, nifedipine. RESULTS: Neocortical blocks generated both recurrent, spontaneous ILEs and interictal-like events under low-Mg2+ artificial CSF (aCSF) perfusion, distinct from those generated in the hippocampus. ILEs from the hippocampus displayed lower thresholds and longer durations as compared with isolated neocortical blocks. Similar results were obtained during 4-AP perfusion. Perfusion with low-Ca2+ ACSF did not produce stereotypical ILEs in the neocortical block, producing instead recurrent, slow depolarizations. Both ILEs and recurrent, slow depolarizations were produced in the hippocampus. Application of APV and nifedipine exacerbated low Mg(2+)-induced ILEs in the hippocampus but not the neocortex, indicating a distinct pharmacology for partial seizures of different brain regions. CONCLUSIONS: The developing mouse hippocampus demonstrates increased ictogenesis compared with the developing neocortex in vitro, consistent with clinical observations and in vivo experimental models.


Assuntos
Hipocampo/efeitos dos fármacos , Hipocampo/crescimento & desenvolvimento , Neocórtex/efeitos dos fármacos , Neocórtex/crescimento & desenvolvimento , Convulsões/induzido quimicamente , 2-Amino-5-fosfonovalerato/farmacologia , 6-Ciano-7-nitroquinoxalina-2,3-diona/farmacologia , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Convulsivantes/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Epilepsia do Lobo Temporal/induzido quimicamente , Epilepsia do Lobo Temporal/fisiopatologia , Potenciais Evocados/efeitos dos fármacos , Potenciais Evocados/fisiologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/crescimento & desenvolvimento , Lobo Frontal/fisiopatologia , Lateralidade Funcional/efeitos dos fármacos , Lateralidade Funcional/fisiologia , Hipocampo/fisiopatologia , Hipocalcemia/fisiopatologia , Técnicas In Vitro , Deficiência de Magnésio/líquido cefalorraquidiano , Deficiência de Magnésio/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Neocórtex/fisiopatologia , Nifedipino/farmacologia , Convulsões/fisiopatologia , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/fisiologia
15.
Epilepsia ; 46(8): 1198-204, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16060928

RESUMO

PURPOSE: The pentylenetetrazol (PTZ) infusion test was used to compare seizure thresholds in adult and young rats fed either a 4:1 ketogenic diet (KD) or a 6.3:1 KD. We hypothesized that both KDs would significantly elevate seizure thresholds and that the 4:1 KD would serve as a better model of the KD used clinically. METHODS: Ninety adult rats and 75 young rats were placed on one of five experimental diets: (a) a 4:1 KD, (b) a control diet balanced to the 4:1 KD, (c) a 6.3:1 KD, (d) a standard control diet, or (e) an ad libitum standard control diet. All subjects were seizure tested by using the PTZ infusion test. Blood glucose and beta-hydroxybutyrate (beta-OHB) levels were measured. RESULTS: Neither KD elevated absolute "latencies to seizure" in young or adult rats. Similarly, neither KD elevated "threshold doses" in adult rats. In young rats, the 6.3:1 KD, but not the 4:1 KD, significantly elevated threshold doses. The 6.3:1 KD group showed poorer weight gain than the 4:1 KD group when compared with respective controls. The most dramatic discrepancies were seen in young rats. CONCLUSIONS: "Threshold doses" and "latency to seizure" data provided conflicting measures of seizure threshold. This was likely due to the inflation of threshold doses calculated by using the much smaller body weights found in the 6.3:1 KD group. Ultimately, the PTZ infusion test in rats may not be a good preparation to model the anticonvulsant effects of the KD seen clinically, especially when dietary treatments lead to significantly mismatched body weights between the groups.


Assuntos
Cetose/metabolismo , Pentilenotetrazol/farmacologia , Convulsões/dietoterapia , Convulsões/prevenção & controle , Ácido 3-Hidroxibutírico/sangue , Fatores Etários , Animais , Glicemia/análise , Peso Corporal/fisiologia , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Cetose/induzido quimicamente , Masculino , Pentilenotetrazol/administração & dosagem , Distribuição Aleatória , Ratos , Ratos Wistar , Convulsões/induzido quimicamente , Resultado do Tratamento
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