Electroconvulsive seizure increases adult hippocampal angiogenesis rats

ArticleinEuropean Journal of Neuroscience 24(3):819-28 · September 2006with5 Reads
DOI: 10.1111/j.1460-9568.2006.04958.x · Source: PubMed
Electroconvulsive seizure has a proven therapeutic application in the treatment of severe depression and treatment-resistant depression. Despite the efficacy of electroconvulsive seizure as a non-chemical antidepressant treatment, the mechanism of action is unclear. Elevation in hippocampal trophic factor expression and concomitant cellular proliferation are thought to play a role in its action. We examined whether the reported induction of angiogenic factors and endothelial cell proliferation leads to an increase in vascular density. Two hippocampal regions, the dentate gyrus and the stratum lacunosum moleculare (SLM), were examined employing a combination of vascular density quantification, angiogenic gene expression analysis and immunohistochemistry. A 6% increase in vascular density was observed in the dentate gyrus but this did not achieve statistical significance. The SLM of the hippocampus exhibited a robust 20-30% increase in vascular density and was accompanied by an increase in expression of inhibitor of differentiation-3. There was also an induction of the angiogenesis markers alphaVbeta3 integrin and Del1. Increases in the vascular density of the SLM could be in response to enhanced metabolic activity in this region. This is supported by the induction of glutamine synthetase and the glutamate transporter GLT1.
    • "Based on these findings, we presume that ECS may cause neuronal cell death, while ECS also induces neurogenesis to replace the death neuron. Not only neurogenesis, studies on the normal rodent brain have also shown that ECS increases angiogenesis [80, 81]. Accordingly, ECS may also induce neurogenesis and angiogenesis even in the pathological hippocampi of Gunn rats. "
    [Show abstract] [Hide abstract] ABSTRACT: Background: Although electroconvulsive therapy (ECT) is regarded as one of the efficient treatments for intractable psychiatric disorders, the mechanism of therapeutic action remains unclear. Recently, many studies indicate that ECT affects the immune-related cells, such as microglia, astrocytes, and lymphocytes. Moreover, microglial activation and astrocytic activation have been implicated in the postmortem brains of schizophrenia patients. We previously demonstrated that Gunn rats showed schizophrenia-like behavior and microglial activation in their brains. The present study examined the effects of electroconvulsive shock (ECS), an animal counterpart of ECT, on schizophrenia-like behavior, microgliosis, and astrogliosis in the brain of Gunn rats. Methods: The rats were divided into four groups, i.e., Wistar sham, Wistar ECS, Gunn sham, and Gunn ECS. ECS groups received ECS once daily for six consecutive days. Subsequently, prepulse inhibition (PPI) test was performed, and immunohistochemistry analysis was carried out to determine the activation degree of microglia and astrocytes in the hippocampus by using anti-CD11b and anti-glial fibrillary acidic protein (GFAP) antibody, respectively. Results: We found PPI deficit in Gunn rats compared to Wistar rats, and it was significantly improved by ECS. Immunohistochemistry analysis revealed that immunoreactivity of CD11b and GFAP was significantly increased in Gunn rats compared to Wistar rats. ECS significantly attenuated the immunoreactivity of both CD11b and GFAP in Gunn rats. Conclusions: ECS ameliorated schizophrenia-like behavior of Gunn rats and attenuated microgliosis and astrogliosis in the hippocampus of Gunn rats. Accordingly, therapeutic effects of ECT may be exerted, at least in part, by inhibition of glial activation. These results may provide crucial information to elucidate the role of activated glia in the pathogenesis of schizophrenia and to determine whether future therapeutic interventions should attempt to up-regulate or down-regulate glial functions.
    Full-text · Article · Sep 2016
    • "We found an increase in the total length of the microvessels in FSL rats 1 week after ketamine treatment. It has been shown that ECS has a prominent effect on increasing the vascular density in the stratum lacunosum molecular region of the hippocampus (Newton et al., 2006). Taken together, our findings were in agreement with this observation and we found a positive correlation between the number of neurons in the granular cell layer of DG and length density of the microvessels in the molecular layer of DG after ketamine treatment. "
    [Show abstract] [Hide abstract] ABSTRACT: Glutamatergic system and the structural plasticity hypothesis are principal components for rapid and sustained antidepressant effects of novel antidepressant therapeutics. This study represents the first investigation of the structural plasticity of the hippocampus as one of the main contributed mechanisms to the sustained anti-depressive effect of ketamine. Flinders Sensitive Line (FSL) and Flinders Resistant Line (FRL) rats were given a single intraperitoneal injection of ketamine (15 mg/kg) or saline 7 days before perfusion-fixed. The optical fractionator method was used to estimate the total number of neurons in the granular cell layer. Microvessel length in the molecular layer of DG was evaluated with global spatial sampling method. By use of the physical disector method, the number of synapses was estimated. The volume of the hippocampus was larger in the FRL-vehicle rats compared with FSL-vehicle group and in FSL-ketamine versus FSL-vehicle rats (P < 0.05). The number of non-perforated synapses was significantly higher in the FSL-ketamine versus FSL-vehicle group, (P = 0.01). A significant effect of ketamine on enhancement of the number of neurons in DG in FSL rats was observed (P = 0.01). The total length of the microvessels 1 week after ketamine treatment in the FSL rats significantly increased (P < 0.05). Our results indicate that neurovascular changes of hippocampus could be one of the possible mechanisms underlying the sustained antidepressant effect of ketamine by reversing alteration of the number of the excitatory synapses, neuronal number and length of the microvessels in the hippocampus. © 2016 Wiley Periodicals, Inc.
    Article · Jul 2016
    • "Whiteus et al. (2014) found a severe reduction of angiogenesis in the cerebral cortex following either vigorous locomotor exercise, persistent auditory stimulation, or chemically induced seizures. In the adult rat brain, however, previous studies using similar hyperactivation paradigms evidenced increased angiogenesis in the cerebellum following intense locomotor exercise (Isaacs et al. 1992) or in the hippocampus after electroconvulsive seizures (Newton et al. 2006), emphasizing the difference between the immature and mature brain in terms of vascular plasticity. Importantly, this angiogenic capability of the adult brain might be relevant in ischemic conditions such as stroke. "
    [Show abstract] [Hide abstract] ABSTRACT: The brain, which represents 2% of body mass but consumes 20% of body energy at rest, has a limited capacity to store energy and is therefore highly dependent on oxygen and glucose supply from the blood stream. Normal functioning of neural circuits thus relies on adequate matching between metabolic needs and blood supply. Moreover, not only does the brain need to be densely vascularized, it also requires a tightly controlled environment free of toxins and pathogens to provide the proper chemical composition for synaptic transmission and neuronal function. In this review, we focus on three major factors that ensure optimal brain perfusion and function: the patterning of vascular networks to efficiently deliver blood and nutrients, the function of the blood–brain barrier to maintain brain homeostasis, and the regulation of cerebral blood flow to adequately couple energy supply to neural function.
    Full-text · Article · Jul 2015
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