RESUMEN
Delivery of melatonin and targeting melatonin receptors pose as neuroprotective strategies for stroke therapy. The potential of melatonin-based therapeutics for clinical application in stroke patients requires translational research to guide the conduct of clinical trials. We review recent preclinical and clinical data that support the use of melatonin for stroke.
Asunto(s)
Melatonina/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Ensayos Clínicos como Asunto , Humanos , Receptores de Melatonina/efectos de los fármacosRESUMEN
Traumatic brain injury (TBI), often called the signature wound of Iraq and Afghanistan wars, is characterized by a progressive histopathology and long-lasting behavioral deficits. Treatment options for TBI are limited and patients are usually relegated to rehabilitation therapy and a handful of experimental treatments. Stem cell-based therapies offer alternative treatment regimens for TBI, and have been intended to target the delayed therapeutic window post-TBI, in order to promote "neuroregeneration," in lieu of "neuroprotection" which can be accomplished during acute TBI phase. However, these interventions may require adjunctive pharmacological treatments especially when aging is considered as a comorbidity factor for post-TBI health outcomes. Here, we put forward the concept that a combination therapy of human umbilical cord blood cell (hUCB) and granulocyte-colony stimulating factor (G-CSF) attenuates neuroinflammation in TBI, in view of the safety and efficacy profiles of hUCB and G-CSF, their respective mechanisms of action, and efficacy of hUCB+G-CSF combination therapy in TBI animal models. Further investigations on the neuroinflammatory pathway as a key pathological hallmark in acute and chronic TBI and also as a major therapeutic target of hUCB+G-CSF are warranted in order to optimize the translation of this combination therapy in the clinic.
Asunto(s)
Envejecimiento/fisiología , Lesiones Encefálicas/tratamiento farmacológico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Inflamación/tratamiento farmacológico , Células Madre , Animales , Comorbilidad , Humanos , Inflamación/epidemiologíaRESUMEN
Cell transplantation has been shown to be an effective therapy for central nervous system disorders in animal models. Improving the efficacy of cell transplantation depends critically on improving grafted cell survival. We investigated whether glial cell line-derived neurotrophic factor (GDNF)-pretreatment of neural stem cells (NSCs) enhanced grafted cell survival in a rat model of Parkinson's disease (PD). We first examined the neuroprotective effects of GDNF on oxygen-glucose deprivation (OGD) in NSCs. Cells were pretreated with GDNF for 3 days before subjecting them to OGD. After 12h of OGD, GDNF-pretreated NSCs showed significant increases in survival rates compared with PBS-pretreated NSCs. An apoptosis assay showed that the number of apoptotic cells was significantly decreased in GDNF-pretreated NSCs at 1h and 6h after OGD. A PD rat model was then established by unilateral injection of 6-hydroxydopamine (6-OHDA, 9µg) into the medial forebrain bundle. Two weeks after 6-OHDA injection, GDNF-pretreated NSCs, PBS-pretreated NSCs, or PBS were injected into PD rat striatum. The survival of grafted cells in the striatum was significantly increased in the GDNF-pretreated NSC group compared with the control groups. GDNF pretreatment increased survival of NSCs following transplantation, at least partly through suppression of cell apoptosis.
Asunto(s)
Factor Neurotrófico Derivado de la Línea Celular Glial/farmacología , Supervivencia de Injerto/fisiología , Células-Madre Neurales/trasplante , Trastornos Parkinsonianos/cirugía , Trasplante de Células Madre/métodos , Animales , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Células Cultivadas , Modelos Animales de Enfermedad , Femenino , Factor Neurotrófico Derivado de la Línea Celular Glial/fisiología , Supervivencia de Injerto/efectos de los fármacos , Ratones , Ratones Endogámicos ICR , Células-Madre Neurales/efectos de los fármacos , Células-Madre Neurales/fisiología , Fármacos Neuroprotectores/farmacología , Neurotoxinas/toxicidad , Oxidopamina/toxicidad , Trastornos Parkinsonianos/inducido químicamente , Trastornos Parkinsonianos/fisiopatología , Embarazo , Ratas , Ratas Sprague-Dawley , Trasplante Heterólogo/métodosRESUMEN
It has been reported that hepatitis C virus (HCV) causes not only liver disease but also disorders of other organs and tissues. Previously, many HCV-related extrahepatic manifestations have been reported. In this study, we report 2 patients in whom tongue cancer was detected during the treatment of HCV-related liver disease. In one patient, tongue cancer was detected during the treatment of HCV-related liver cirrhosis, and articular rheumatism developed thereafter. The duration of HCV-related liver disease was 10 years. In the other patient, tongue cancer was detected during the treatment of HCV-related hepatocellular carcinoma. This patient had a past history of thyroid disease. The duration of HCV-related liver disease was 6 years. In these patients, the possibility that several conditions incidentally and concurrently developed cannot be denied. However, the conditions described above may be regarded as HCV-related extra-hepatic manifestations. In patients with HCV infection, it is important to examine conditions in organs other than the liver. Careful follow-up is needed.
Asunto(s)
Artritis Reumatoide/etiología , Enfermedades Autoinmunes/etiología , Carcinoma de Células Escamosas/etiología , Hepatitis C Crónica/complicaciones , Hipotiroidismo/etiología , Neoplasias de la Lengua/etiología , Anciano , Carcinoma Hepatocelular/etiología , Femenino , Humanos , Cirrosis Hepática/etiología , Neoplasias Hepáticas/etiología , Persona de Mediana EdadRESUMEN
We report a correlation between P300 and cerebral blood flow in 11 patients with chronic moderate alcoholism. The patients had been drinking more than 83 ml pure alcohol equivalent everyday for more than 10 years and did not have any other neurological diseases. The P300 latency was significantly longer in the chronic alcoholism group than in the age-matched healthy control group. There was a significant negative correlation between the P300 latency and the thalamus blood flow in the chronic alcoholism group. These findings suggest that there is a subclinical disturbance of cognitive function in chronic alcoholism and that the prolongation of P300 latency is related to the decrease in thalamus blood flow in chronic alcoholism.
Asunto(s)
Alcoholismo/fisiopatología , Circulación Cerebrovascular/fisiología , Potenciales Relacionados con Evento P300/fisiología , Anciano , Humanos , Persona de Mediana Edad , Flujo Sanguíneo RegionalRESUMEN
A 45-year-old man noticed mild numbness of the feet at the age of 40 years and difficulty in standing up from squatting position at 43 years. His birth and developmental milestones were normal and the family history was unremarkable. He was alert and intelligent with global IQ of 91. There was mild muscle weakness as well as atrophy in bilateral hips and thighs. The serum creatine kinase level was 542 U/l. On computed tomography, the hamstrings were preferentially involved. The biopsied specimens from the right quadriceps femoris and peroneal muscles showed myogenic changes with evidence of necrotic and regenerating process. Dystrophin, dystrophin-associated glycoproteins and merosin were normally expressed. From the clinical and pathologic findings, he was diagnosed as having myopathy. The electroencephalogram was normal but the P300 latency was prolonged. T2-weighted head magnetic resonance imaging showed diffuse high intensity in the cerebral white matter. Myopathy with cerebral white matter abnormality in adult patients has not yet been reported. Asymptomatic cerebral white matter abnormality should be considered in adult patients with myopathy.