VEGF Modulates Neurogenesis and Microvascular Remodeling in Epileptogenesis After Status Epilepticus in Immature Rats

Han, Wei; Jiang, Li; Song, Xiaojie; Li, Tianyi; Chen, Hengsheng; Cheng, Li

doi:10.3389/fneur.2021.808568

Cited by 10 publications

(3 citation statements)

References 49 publications

(61 reference statements)

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“…Enhanced expression of vascular endothelial growth factor (VEGF) has been reported in hippocampal slices from patients with drug-resistant epilepsy [ 37 ]. Consistently, reduced cerebral blood flow and tissue hypoxia can trigger an increased expression of VEGF in vascular endothelial cells, thus inducing abnormal angiogenesis and increasing microvascular structural density during epileptogenesis [ 38 ]. It is suggested that this adaptative process may improve perfusion and meet the heightened metabolic demands of neurons.…”

Section: Changes Of the Neurovascular Unit In Epileptogenesismentioning

confidence: 99%

The Neurovascular Unit Dysfunction in the Molecular Mechanisms of Epileptogenesis and Targeted Therapy

Liu,

Zhang,

Zhao

et al. 2024

Neurosci. Bull.

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Epilepsy is a multifaceted neurological syndrome characterized by recurrent, spontaneous, and synchronous seizures. The pathogenesis of epilepsy, known as epileptogenesis, involves intricate changes in neurons, neuroglia, and endothelium, leading to structural and functional disorders within neurovascular units and culminating in the development of spontaneous epilepsy. Although current research on epilepsy treatments primarily centers around anti-seizure drugs, it is imperative to seek effective interventions capable of disrupting epileptogenesis. To this end, a comprehensive exploration of the changes and the molecular mechanisms underlying epileptogenesis holds the promise of identifying vital biomarkers for accurate diagnosis and potential therapeutic targets. Emphasizing early diagnosis and timely intervention is paramount, as it stands to significantly improve patient prognosis and alleviate the socioeconomic burden. In this review, we highlight the changes and molecular mechanisms of the neurovascular unit in epileptogenesis and provide a theoretical basis for identifying biomarkers and drug targets.

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Section: Changes Of the Neurovascular Unit In Epileptogenesismentioning

confidence: 99%

The Neurovascular Unit Dysfunction in the Molecular Mechanisms of Epileptogenesis and Targeted Therapy

Liu,

Zhang,

Zhao

et al. 2024

Neurosci. Bull.

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“…Another target of HIF activity in reactive neonatal astrocytes that contributes to enhancing endogenous restorative mechanisms is VEGF, the aforementioned factor that stimulates the formation of new blood vessels to compensate for oxygen deficiencies in the affected nervous tissue. However, as demonstrated by numerous in vitro and in vivo studies, VEGF can promote neurogenesis [95][96][97][98], directly supporting tissue repair. In this context, the induced astrocytic reactivity associated with HIF activation is beneficial for neuroregeneration.…”

Section: Astrocyte Reactivity In Neurodevelopmental Disordersmentioning

confidence: 99%

Reactive Gliosis in Neonatal Disorders: Friend or Foe for Neuroregeneration?

Gargas,

Janowska,

Gebala

et al. 2024

Cells

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A developing nervous system is particularly vulnerable to the influence of pathophysiological clues and injuries in the perinatal period. Astrocytes are among the first cells that react to insults against the nervous tissue, the presence of pathogens, misbalance of local tissue homeostasis, and a lack of oxygen and trophic support. Under this background, it remains uncertain if induced astrocyte activation, recognized as astrogliosis, is a friend or foe for progressing neonatal neurodevelopment. Likewise, the state of astrocyte reactivity is considered one of the key factors discriminating between either the initiation of endogenous reparative mechanisms compensating for aberrations in the structures and functions of nervous tissue or the triggering of neurodegeneration. The responses of activated cells are modulated by neighboring neural cells, which exhibit broad immunomodulatory and pro-regenerative properties by secreting a plethora of active compounds (including interleukins and chemokines, neurotrophins, reactive oxygen species, nitric oxide synthase and complement components), which are engaged in cell crosstalk in a paracrine manner. As the developing nervous system is extremely sensitive to the influence of signaling molecules, even subtle changes in the composition or concentration of the cellular secretome can have significant effects on the developing neonatal brain. Thus, modulating the activity of other types of cells and their interactions with overreactive astrocytes might be a promising strategy for controlling neonatal astrogliosis.

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“…Within this region of the brain, increased levels of VEGF promote neurogenesis and microvascular remodeling, amongst other beneficial effects. This could have implications for a variety of conditions including status epilepticus and Alzheimer's disease [34][35][36]. Within the eye, it was shown that VEGF conferred some degree of neuroprotection against dry eye disorders.…”

Section: Neuroprotective Effects Of Omega-3 Fatty Acidsmentioning

confidence: 99%

Omega-3 Polyunsaturated Fatty Acids and Their Anti-Oxidant, Anti-Inflammatory and Neuroprotective Effects in Diabetic Retinopathy: A Narrative Review

Fathima¹,

Prokopiou²,

Georgiou³

2023

Front. Biosci. (Landmark Ed)

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Diabetic retinopathy (DR) is a common microvascular complication of type 2 Diabetes Mellitus (T2DM) that can have vision-threatening consequences, particularly if it advances to the proliferative stage and is left untreated. Owing to the central role of hyperglycemia-induced oxidative stress, multiple anti-oxidants have been investigated for their therapeutic value. However, there is a lack of substantial data to support the use of any of the compounds tested so far. Omega-3 polyunsaturated fatty acids (PUFAs), namely docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have received much acclaim for their positive impact on cardiovascular health outcomes. The anti-oxidative, anti-inflammatory and neuroprotective properties of PUFAs also make them promising therapeutic and preventive agents for DR. The current evidence is derived mainly from in vitro and animal studies and provides some insight into the underlying mechanisms involved. These fatty acids are capable of direct anti-oxidative and anti-inflammatory effects. They also concomitantly promote intrinsic defense mechanisms and recovery, particularly of photoreceptor neurons. Hence, dietary supplementation with PUFAs, mainly from marine sources, can halt and reverse the retinal damage seen in DR. Furthermore, clinical trials have reported improved vision and quality of life in DR patients after supplementation. However, a major limitation of these trials is the use of nutraceutical formulations in which omega-3 PUFAs are combined with other anti-oxidant compounds, thereby preventing the evaluation of omega-3 as standalone treatment. Although the results of experimental studies to date have been promising, more clinical trials are required to determine the full extent of benefits in patients with DR.

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VEGF Modulates Neurogenesis and Microvascular Remodeling in Epileptogenesis After Status Epilepticus in Immature Rats

Cited by 10 publications

References 49 publications

The Neurovascular Unit Dysfunction in the Molecular Mechanisms of Epileptogenesis and Targeted Therapy

The Neurovascular Unit Dysfunction in the Molecular Mechanisms of Epileptogenesis and Targeted Therapy

Reactive Gliosis in Neonatal Disorders: Friend or Foe for Neuroregeneration?

Omega-3 Polyunsaturated Fatty Acids and Their Anti-Oxidant, Anti-Inflammatory and Neuroprotective Effects in Diabetic Retinopathy: A Narrative Review

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