RESUMO
Despite continuous improvement in neonatology there is no clinically effective treatment for perinatal hypoxia ischemia (HI). Therefore, development of a new therapeutic intervention to minimize the resulting neurological consequences is urgently needed. The immature brain is highly responsive to environmental stimuli, such as environmental enrichment but a more effective paradigm is enriched rehabilitation (ER), which combines environmental enrichment with daily reach training. Another neurorestorative strategy to promote tissue repair and functional recovery is cyclosporine A (CsA). However, potential benefits of CsA after neonatal HI have yet to be investigated. The aim of this study was to investigate the effects of a combinational therapy of CsA and ER in attempts to promote cognitive and motor recovery in a rat model of perinatal hypoxic-ischemic injury. Seven-day old rats were submitted to the HI procedure and divided into 4 groups: CsA+Rehabilitation; CsA+NoRehabilitation; Vehicle+Rehabilitation; Vehicle+NoRehabilitation. Behavioural parameters were evaluated pre (experiment 1) and post 4 weeks of combinational therapy (experiment 2). Results of experiment 1 demonstrated reduced open field activity of HI animals and increased foot faults relative to shams in the ladder rung walking test. In experiment 2, we showed that ER facilitated acquisition of a staircase skilled-reaching task, increased number of zone crosses in open-field exploration and enhanced coordinated limb use during locomotion on the ladder rung task. There were no evident deficits in novel object recognition testing. Delayed administration of CsA, had no effect on functional recovery after neonatal HI. There was a significant reduction of cortical and hemispherical volume and hippocampal area, ipsilateral to arterial occlusion in HI animals; combinational therapy had no effect on these morphological measurements. In conclusion, the present study demonstrated that ER, but not CsA was the main contributor to enhanced recovery of motor ability after neonatal HI.
Assuntos
Meio Ambiente , Hipóxia-Isquemia Encefálica/fisiopatologia , Hipóxia-Isquemia Encefálica/reabilitação , Atividade Motora/fisiologia , Recuperação de Função Fisiológica/fisiologia , Fatores Etários , Animais , Animais Recém-Nascidos , Infarto Encefálico/tratamento farmacológico , Infarto Encefálico/etiologia , Infarto Encefálico/reabilitação , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/reabilitação , Ciclosporina/uso terapêutico , Comportamento Exploratório/efeitos dos fármacos , Comportamento Exploratório/fisiologia , Comportamento Alimentar/efeitos dos fármacos , Comportamento Alimentar/fisiologia , Feminino , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Imunossupressores/uso terapêutico , Masculino , Gravidez , Desempenho Psicomotor/efeitos dos fármacos , Desempenho Psicomotor/fisiologia , Ratos , Ratos Sprague-Dawley , Reconhecimento Psicológico/efeitos dos fármacos , Reconhecimento Psicológico/fisiologia , Recuperação de Função Fisiológica/efeitos dos fármacosRESUMO
OBJECTIVES: To examine the natural clinical course of patients admitted to inpatient neurorehabilitation in a coma, vegetative state (VS), or minimally conscious state (MCS) after anoxic-ischaemic encephalopathy (AIE). METHODS: This is a retrospective cohort study of 113 consecutive patients admitted to a German inpatient neurorehabilitation centre with severe disorders of consciousness (DOC) following AIE due to cardiac arrest over a 6-year period. Functional independence was measured with the Glasgow Outcome Scale (GOS) and recovery of consciousness with the Coma Remission Scale (CRS). Separate binary logistic regression models were used to identify independent predictors for functional and behavioural outcomes. RESULTS: Seven patients (6.2%) achieved a good functional outcome (GOS 4-5). Five of these showed significant functional improvement within the first 8 weeks. 22 patients (19.5%) recovered consciousness; the last patient began to make significant improvement between weeks 10 and 12. Logistic regression showed that both increasing age and lower admission CRS predicted unfavourable functional outcome and persistent DOC. A longer stay in the ICU also predicted persistent DOC at the end of neurorehabilitation. However, neither malignant somatosensory evoked potential (SEP) test results nor hypothermia treatment on the ICU were outcome predictors in either outcome category. CONCLUSION: Even among severely affected AIE patients arriving at a neurological rehabilitation centre in a DOC, there remains potential for functional and behavioural improvement. However, significant improvements may not begin for up to 3 months post-injury. This study suggests that recovery of consciousness and even a good neurological outcome are possible despite malignant SEP test results.
Assuntos
Coma/reabilitação , Hipóxia-Isquemia Encefálica/reabilitação , Estado Vegetativo Persistente/reabilitação , Adulto , Estudos de Coortes , Coma/etiologia , Feminino , Humanos , Hipóxia-Isquemia Encefálica/complicações , Masculino , Pessoa de Meia-Idade , Estado Vegetativo Persistente/etiologia , Estudos Retrospectivos , Sobreviventes , Fatores de Tempo , Resultado do TratamentoRESUMO
We have examined 89 newborns with perinatal CNS lesions due to critical states at birth. Disturbances of vital functions of the organism developed as a result of severe posthypoxia states at birth that exert a significant effect on patient's quality of life in the following age periods, including the formation of "rough" polyorganic injuries, have been studied. Therefore, the adequate treatment of post-critical states in the neonatal period demands understanding of pathogenetic mechanisms of their development that has formed the basis for using peptide drugs with neuroprotective effect, in particular, cortexin.