Epilepsia secundaria a encefalitis por el virus de Epstein Barr / Epilepsy secondary to encephalitis due to Epstein Barr virus

Presentación del caso. Se trata de una mujer de 44 años de edad, con historia de cefalea occipital, lenguaje incoherente y pensamiento confuso. Inicialmente presentaba diez puntos en la escala de Glasgow y una hemiparesia izquierda. La tomografía computarizada de cráneo, reportó edema cerebral con lesión hipodensa talámica derecha y deterioro neurológico progresivo.El electroencefalograma evidenció desaceleración unilateral hemisférica derecha. El estudio del líquido cefalorraquídeo describió hiperproteinorraquia y un recuento a predominio linfocitario de 450 células con glucorraquia conservada, sin presencia de bacterias. Intervención terapéutica. se manejó con soporte ventilatorio invasivo y con tratamiento antibiótico y antiviral a dosis meníngeas, además de anticonvulsivantes. Los hallazgos tomográficos de control reportaron una hidrocefalia; se colocó una derivación ventricular tipo Becker. La serología IgM resultó positiva para virus de Epstein Barr y se identificó el genoma viral en el líquido cefalorraquídeo, a través de la prueba de reacción en cadena de polimerasa. La tomografía cerebral de control, evidenció la persistencia de la ventriculomegalia y de edema cerebral, lo que generó el diagnóstico de una encefalitis de etiología viral complicada con epilepsia secundaria por una lesión estructural desmielinizante del hemisferio cerebral derecho. Evolución clínica. La intervención terapéutica con inmunoglobulina intravenosa generó una mejoría del estado general. Fue posible retirar la derivación ventricular y la ventilación pulmonar diez y 19 días después del ingreso, respectivamente. La paciente se encuentra actualmente en fisioterapia con persistencia de hemiparesia izquierda, alteraciones de la marcha, disartria y episodios convulsivos controlados durante los últimos seis meses

Case presentation. This case is about a 44 years old woman with a history of occipital headache, incoherent speech and confused thinking. She initially presented ten points on the Glasgow scale and left hemiparesis. Cranial CT scan reported cerebral edema with right thalamic hypodense lesion and progressive neurological deterioration. The electroencephalogram showed unilateral right hemispheric deceleration. The cerebrospinal fluid study showed hyperproteinuria and a predominantly lymphocyte count of 450 cells with preserved glycorrhachia, without the presence of bacteria. Treatment.was managed with invasive ventilatory support and antibiotic and antiviral treatment at meningeal doses, in addition to anticonvulsants. Control tomographic findings showed hydrocephalus; a Becker type ventricular shunt was placed. IgM serology was positive for Epstein Barr virus and the viral genome was identified in the cerebrospinal fluid by polymerase chain reaction test. The control brain tomography showed persistent ventriculomegaly and cerebral edema, which led to the diagnosis of encephalitis of viral etiology complicated by epilepsy secondary to a demyelinating structural lesion of the right cerebral hemisphere. Outcome. Therapeutic intervention with intravenous immunoglobulin was performed with improvement of the general condition, it was possible to remove the ventricular shunt and pulmonary ventilation ten and 19 days after admission, respectively. The patient is currently in physical therapy with persistence of left hemiparesis, gait disturbances, dysarthria, and controlled convulsive episodes during the last six months.

Regulation of Diabetes: a Therapeutic Strategy for Alzheimer's Disease?

Accumulated evidence suggests that sporadic cases of Alzheimer's disease (AD) make up more than 95% of total AD patients, and diabetes has been implicated as a strong risk factor for the development of AD. Diabetes shares pathological features of AD, such as impaired insulin signaling, increased oxidative stress, increased amyloid-beta (Aβ) production, tauopathy and cerebrovascular complication. Due to shared pathologies between the two diseases, anti-diabetic drugs may be a suitable therapeutic option for AD treatment. In this article, we will discuss the well-known pathologies of AD, including Aβ plaques and tau tangles, as well as other mechanisms shared in AD and diabetes including reactive glia and the breakdown of blood brain barrier in order to evaluate the presence of any potential, indirect or direct links of pre-diabetic conditions to AD pathology. In addition, clinical evidence of high incidence of diabetic patients to the development of AD are described together with application of anti-diabetic medications to AD patients.

Structural optimization and biological evaluation of 1,5-disubstituted pyrazole-3-carboxamines as potent inhibitors of human 5-lipoxygenase

Human 5-lipoxygenase (5-LOX) is a well-validated drug target and its inhibitors are potential drugs for treating leukotriene-related disorders. Our previous work on structural optimization of the hit compound 2 from our in-house collection identified two lead compounds, 3a and 3b, exhibiting a potent inhibitory profile against 5-LOX with IC50 values less than 1 µmol/L in cell-based assays. Here, we further optimized these compounds to prepare a class of novel pyrazole derivatives by opening the fused-ring system. Several new compounds exhibited more potent inhibitory activity than the lead compounds against 5-LOX. In particular, compound 4e not only suppressed lipopolysaccharide-induced inflammation in brain inflammatory cells and protected neurons from oxidative toxicity, but also significantly decreased infarct damage in a mouse model of cerebral ischemia. Molecular docking analysis further confirmed the consistency of our theoretical results and experimental data. In conclusion, the excellent in vitro and in vivo inhibitory activities of these compounds against 5-LOX suggested that these novel chemical structures have a promising therapeutic potential to treat leukotriene-related disorders.

Brain Inflammation and Microglia: Facts and Misconceptions

The inflammation that accompanies acute injury has dual functions: bactericidal action and repair. Bactericidal functions protect damaged tissue from infection, and repair functions are initiated to aid in the recovery of damaged tissue. Brain injury is somewhat different from injuries in other tissues in two respects. First, many cases of brain injury are not accompanied by infection: there is no chance of pathogens to enter in ischemia or even in traumatic injury if the skull is intact. Second, neurons are rarely regenerated once damaged. This raises the question of whether bactericidal inflammation really occurs in the injured brain; if so, how is this type of inflammation controlled? Many brain inflammation studies have been conducted using cultured microglia (brain macrophages). Even where animal models have been used, the behavior of microglia and neurons has typically been analyzed at or after the time of neuronal death, a time window that excludes the inflammatory response, which begins immediately after the injury. Therefore, to understand the patterns and roles of brain inflammation in the injured brain, it is necessary to analyze the behavior of all cell types in the injured brain immediately after the onset of injury. Based on our experience with both in vitro and in vivo experimental models of brain inflammation, we concluded that not only microglia, but also astrocytes, blood inflammatory cells, and even neurons participate and/or regulate brain inflammation in the injured brain. Furthermore, brain inflammation played by these cells protects neurons and repairs damaged microenvironment but not induces neuronal damage.

Systemic LPS administration induces brain inflammation but not dopaminergic neuronal death in the substantia nigra

It has been suggested that brain inflammation is important in aggravation of brain damage and/or that inflammation causes neurodegenerative diseases including Parkinson's disease (PD). Recently, systemic inflammation has also emerged as a risk factor for PD. In the present study, we evaluated how systemic inflammation induced by intravenous (iv) lipopolysaccharides (LPS) injection affected brain inflammation and neuronal damage in the rat. Interestingly, almost all brain inflammatory responses, including morphological activation of microglia, neutrophil infiltration, and mRNA/protein expression of inflammatory mediators, appeared within 4-8 h, and subsided within 1-3 days, in the substantia nigra (SN), where dopaminergic neurons are located. More importantly, however, dopaminergic neuronal loss was not detectable for up to 8 d after iv LPS injection. Together, these results indicate that acute induction of systemic inflammation causes brain inflammation, but this is not sufficiently toxic to induce neuronal injury.

Protein kinase A mediates microglial activation induced by plasminogen and gangliosides

In the injured brain, microglia is known to be activated and produce proinflammatory mediators such as interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS). We investigated the role of protein kinase A (PKA) in microglial activation by both plasminogen and gangliosides in rat primary microglia and in the BV2 immortalized murine microglial cell line. Both plasminogen and gangliosides induced IL-1beta, TNF-alpha and iNOS mRNA expression, and that this expression was inhibited by the addition of the PKA inhibitors, KT5720 and H89. Both plasminogen and gangliosides activated PKA and increased the DNA binding activity of the cAMP response element- binding protein (CREB). Furthermore, KT5720 and H89 reduced the DNA binding activities of CREB and NF-kappaB in plasminogen-treated cells. These results suggest that PKA plays an important role in plasminogen and gangliosides- induced microglial activation.