Cannula implantation into the lateral ventricle does not adversely affect recognition or spatial working memory.

Indwelling cannulas are often used to deliver pharmacological agents into the lateral ventricles of the brain to study their effects on memory and learning, yet little is known about the possible adverse effects of the cannulation itself. In this study, the effect of implanting an indwelling cannula into the right lateral ventricle was examined with respect to cognitive function and tissue damage in rats. Specifically, the cannula passed through sections of the primary motor (M1) and somatosensory hind limb (S1HL) cortices. One week following implantation, rats were impaired on the rotarod task, implying a deficit in fine motor control, likely caused by the passage of the cannula through the aforementioned cortical regions. Importantly, neither spatial working nor recognition memory was adversely affected. Histological examination showed immune cell activation only in the area immediately surrounding the cannulation site and not spreading to other brain regions. Both GFAP and CD-11b mRNA expression was elevated in the area immediately surrounding the cannulation site, but not in the contralateral hemisphere or the hippocampus. Neither of the inflammatory cytokines, TNF-α or IL-6, were upregulated in any region. These results show that cannulation into the lateral ventricle does not impair cognition and indicates that nootropic agents delivered via this method are enhancing normal memory rather than rescuing deficits caused by the surgery procedure.

Graphene Functionalized Scaffolds Reduce the Inflammatory Response and Supports Endogenous Neuroblast Migration when Implanted in the Adult Brain.

Electroactive materials have been investigated as next-generation neuronal tissue engineering scaffolds to enhance neuronal regeneration and functional recovery after brain injury. Graphene, an emerging neuronal scaffold material with charge transfer properties, has shown promising results for neuronal cell survival and differentiation in vitro. In this in vivo work, electrospun microfiber scaffolds coated with self-assembled colloidal graphene, were implanted into the striatum or into the subventricular zone of adult rats. Microglia and astrocyte activation levels were suppressed with graphene functionalization. In addition, self-assembled graphene implants prevented glial scarring in the brain 7 weeks following implantation. Astrocyte guidance within the scaffold and redirection of neuroblasts from the subventricular zone along the implants was also demonstrated. These findings provide new functional evidence for the potential use of graphene scaffolds as a therapeutic platform to support central nervous system regeneration.

Gsx2 controls region-specific activation of neural stem cells and injury-induced neurogenesis in the adult subventricular zone.

Neural stem cells (NSCs) reside in widespread regions along the lateral ventricle and generate diverse olfactory bulb (OB) interneuron subtypes in the adult mouse brain. Molecular mechanisms underlying their regional diversity, however, are not well understood. Here we show that the homeodomain transcription factor Gsx2 plays a crucial role in the region-specific control of adult NSCs in both persistent and injury-induced neurogenesis. In the intact brain, Gsx2 is expressed in a regionally restricted subset of NSCs and promotes the activation and lineage progression of stem cells, thereby controlling the production of selective OB neuron subtypes. Moreover, Gsx2 is ectopically induced in damaged brains outside its normal expression domains and is required for injury-induced neurogenesis in the subventricular zone (SVZ). These results demonstrate that mobilization of adult NSCs is controlled in a region-specific manner and that distinct mechanisms operate in continuous and injury-induced neurogenesis in the adult brain.

Mechanisms of neurogenesis in the normal and injured adult brain.

Even in the adult brain, new neurons are continuously generated from endogenous neural stem cells that reside in two restricted regions: the subventricular zone (SVZ) of the lateral ventricle and the dentate gyrus of the hippocampus. These new neurons are integrated into the mature neuronal circuitry and become involved in various functions, thereby contributing to structural and functional plasticity in the adult brain. In this review, we summarize our recent findings on the regulatory mechanisms of SVZ neurogenesis under physiological and pathological conditions in various animal models. Some of these findings were presented in the Kitazato Prize Lecture at Keio University School of Medicine in 2011.

Transgressing the ventricular wall during subthalamic deep brain stimulation surgery for Parkinson disease increases the risk of adverse neurological sequelae.

BACKGROUND: Deep brain stimulation (DBS) at the subthalamic nucleus (STN) is an effective treatment for the motor manifestations of advanced medically refractory Parkinson disease. Because of the medial location of the target, surgical trajectories to the STN may violate the ipsilateral lateral ventricle. OBJECTIVE: To determine whether violating the ventricle during STN DBS surgery is associated with postoperative confusion. METHODS: A retrospective chart review of all STN implantation procedures for Parkinson disease performed by 1 surgeon between January 2005 and September 2008 was performed. Postoperative magnetic resonance imaging was performed in all cases, and each scan was reviewed for evidence of ventricular wall violation. All charts were reviewed for postoperative confusion and/or increased length of hospital stay. RESULTS: A total of 145 leads were implanted in 81 patients over 102 admissions. Forty-three patients underwent contemporaneous bilateral lead implantation; 23 underwent unilateral implantation; and 18 underwent staged bilateral implantation. The cases of 8 patients were complicated by postoperative confusion and increased length of stay. Sixteen magnetic resonance imaging scans demonstrated evidence of ventricular wall violation including all 8 patients with postoperative confusion. The relative risk of having postoperative confusion after traversing the ventricle is 87 (P < .001). CONCLUSION: Violating the ventricular system during STN DBS surgery correlated significantly with postoperative altered mental status and subsequent increased length of hospital stay. This finding may explain why cognitive complications are observed more frequently in Parkinson disease patients undergoing DBS at the STN compared with the internal globus pallidus.

Hippocampal θ dysfunction after lateral fluid percussion injury.

Chronic memory deficits are a major cause of morbidity following traumatic brain injury (TBI). In the rat, the hippocampal theta rhythm is a well-studied correlate of memory function. This study sought to investigate disturbances in hippocampal theta rhythm following lateral fluid percussion injury in the rat. A total of 13 control rats and 12 TBI rats were used. Electrodes were implanted in bilateral hippocampi and an electroencephalogram (EEG) was recorded while the rats explored a new environment, and also while navigating a modified version of the Barnes maze. Theta power and peak theta frequency were significantly attenuated in the injured animals. Further, injured rats were less likely to develop a spatial strategy for Barnes maze navigation compared to control rats. In conclusion, rats sustaining lateral fluid percussion injury demonstrated deficits in hippocampal theta activity. These deficits may contribute to the underlying memory problems seen in chronic TBI.

Computarised brain tomography in patients with schizophrenia

Se práctico la tomografía cerebral de 27 pacientes con esquizofrenia y 17 sujetos controles normales. Los criterios del DSM-IV se utiilzaron para el diagnóstico. Los parámetros usados fueron los siguientes: volumen cerebral, ventrículos laterales y tercer ventrículo, superficie crerebral y los índices cerebrales. Los pacientes fueron evaluados previamente con las siguientes escalas clinicas: Escala de los Síntomas Positivos y Negativos (PANSS), la Escala Breve de Evaluación Psiquiátrica (BPRS), la Escala de Funcionamiento Global (GAF) y la Sscala de GRAFFAR para evaluar los niveles culturales y socioeconómicos. Se detectó un incremento en el cociente entre el tamaño de los ventrículos laterales derecho e izquierdo y el cerebro, un aumento en la anchura de las cisuras de Sylvio y en el índice del tercer ventrículo. No se encontraron diferencias que pudieran relacionarse con el sexo o con la historia familiar de enfermedad mental. Tampoco se observaron diferencias entre el grupo que recibió medicación y el grupo de pacientes no tratados