VEGF treatment during status epilepticus attenuates long-term seizure-associated alterations in astrocyte morphology

Lenzer-Fanara, Janice R.; Li, Thomas; Salerni, E.; Payen, Firmause; Croll, Susan D.

doi:10.1016/j.yebeh.2017.02.019

Cited by 14 publications

(11 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, it should be noted that VEGF/VEGFR signaling also has neurotrophic effects in CNS including the induction of neurite outgrowth and suppression of neuronal death (Rosenstein et al, 2010). Furthermore, several studies have reported that VEGF has antiepileptic effects in pilocarpine-induced SE rats (McCloskey et al, 2005;Han et al, 2017;Lenzer-Fanara et al, 2017). VEGF treatment reduced spontaneous discharges of neurons in brain slices (McCloskey et al, 2005) and promoted hippocampal neurogenesis in vivo, improving recognition ability (Han et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

“…VEGF treatment reduced spontaneous discharges of neurons in brain slices (McCloskey et al, 2005) and promoted hippocampal neurogenesis in vivo, improving recognition ability (Han et al, 2017). Additionally, VEGF treatment changed the morphology of astrocytes, especially their branches (Lenzer-Fanara et al, 2017), which may affect hippocampal function after seizures because astrocytic feet are essential components of tripartite synapse (Figure 1).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Vascular Abnormalities and the Role of Vascular Endothelial Growth Factor in the Epileptic Brain

2020

View full text Add to dashboard Cite

Epilepsy is a chronic neurological disorder generally defined to be caused by excessive neuronal activity. Thus, excessive neuronal activity is the main target of the currently used antiepileptic drugs (AEDs). However, as many as 30% of epileptic patients show drug resistance to currently available AEDs, which suggests that epilepsy should be attributed not only to neuronal cells but also to other brain cells, such as glial cells and vascular cells. Astrocytes, pericytes, and endothelial cells in particular comprise the blood-brain barrier (BBB), which tightly regulates the exchange of substances between the brain parenchyma and the circulating blood. It has been proposed that BBB dysfunction, especially barrier leakage, exacerbates epileptic progression, and conversely, that epileptic seizures induce barrier leakage. Furthermore, several studies have shown that BBB dysfunction is one of the main causes of drug resistance in epilepsy. To better understand the mechanisms that link BBB dysfunction and intractable epilepsy to gain insights for the future development of treatments, we review and discuss the relationships between epilepsy and brain vascular abnormalities, mainly by focusing on vascular malformation, BBB dysfunction, and excessive angiogenesis. Because these abnormalities have been reported to be caused by vascular endothelial growth factor (VEGF) in the ischemic brain, we discuss the possible role of VEGF in vascular abnormalities in the epileptic brain, in which the upregulation of VEGF levels has been reported. Both glial cells and endothelial cells express VEGF receptors (VEGFRs); thus, these cells are likely affected by increases in VEGF during seizures, which in turn could cause vascular abnormalities. In this review, we review the possible role of VEGF in epilepsy and discuss the mechanisms that link vascular abnormalities and intractable epilepsy.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Vascular Abnormalities and the Role of Vascular Endothelial Growth Factor in the Epileptic Brain

2020

View full text Add to dashboard Cite

show abstract

“…VEGF generated by ependymal cells activates and enhances neuronal precursor proliferation and growth in the SCZ and SGZ zones ( Chodobski et al, 2003 ). Moreover, VEGF enhances astrocytes proliferation and migration ( Lenzer-Fanara et al, 2017 ), as well as stimulates growth and survival of Schwann cells after hypoxia ( Cattin et al, 2015 ). Its neurogenesis effect is assessed by stimulation of the endothelium to release neurotrophic factors ( Feng et al, 2012 ).…”

Section: Discussionmentioning

confidence: 99%

Increase in Blood Levels of Growth Factors Involved in the Neuroplasticity Process by Using an Extremely Low Frequency Electromagnetic Field in Post-stroke Patients

Cichoń

Bijak

Czarny

et al. 2018

Front. Aging Neurosci.

View full text Add to dashboard Cite

Background: Neuroplasticity ensures the improvement of functional status in patients after stroke. The aim of this study was to evaluate the effect of extremely low-frequency electromagnetic field therapy (ELF-EMF) on brain plasticity in the rehabilitation of patients after stroke.Methods: Forty-eight patients were divided into two groups underwent the same rehabilitation program, but in the study group, the patients additionally were exposed to a standard series of 10 ELF-EMF treatments. To determine the level of neuroplasticity, we measured the plasma level of the brain-derived neurotrophic factor (BDNF), the vascular-endothelial growth factor, as well as BDNF mRNA expression. Additionally, we determined the molecule levels for hepatocyte growth factor, stem cell factor, stromal cell-derived factor 1α, nerve growth factor β, and leukemia inhibitory factor, using 5plex cytokine panel in plasma. After 4 weeks, during which patients had undergone neurorehabilitation and neurological examinations, we assessed functional recovery using the Barthel Index, Mini-Mental State Examination (MMSE), Geriatric Depression Scale, National Institutes of Health Stroke Scale (NIHSS), and the modified Rankin Scale (mRS).Results: We observed that ELF-EMF significantly increased growth factors and cytokine levels involved in neuroplasticity, as well as promoted an enhancement of functional recovery in post-stroke patients. Additionally, we presented evidence that these effects could be related to the increase of gene expression on the mRNA level. Moreover, a change of BDNF plasma level was positively correlated with the Barthel Index, MMSE, and negatively correlated with GDS.Conclusion: Extremely low-frequency electromagnetic field therapy improves the effectiveness of rehabilitation of post-stroke patients by improving neuroplasticity processes.

show abstract

“…Neurotrophic factors, involved in the survival of neurons as well as in the proliferation and differentiation of neuronal precursors, could be useful as prognosis biomarkers in SE. An upregulation of neurotrophic factors after SE is seen as reflecting a potential neuroprotective role . Moreover, it was shown that FGF‐2/BDNF‐expressing vectors in pilocarpine model of SE were associated with an increased neurogenesis, limited neuronal damage, and reduced occurrence of spontaneous seizures …”

Section: Neurogenesismentioning

confidence: 99%

Cerebrospinal fluid and blood biomarkers of status epilepticus

et al. 2019

View full text Add to dashboard Cite

Status epilepticus is a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms that lead to abnormally prolonged seizures and require urgent administration of antiepileptic drugs. Refractory status epilepticus requires anesthetics drugs and may lead to brain injury with molecular and cellular alterations (eg, inflammation, and neuronal and astroglial injury) that could induce neurologic sequels and further development of epilepsy. Outcome scores based on demographic, clinical, and electroencephalography (EEG) condition are available, allowing prediction of the risk of mortality, but the severity of brain injury in survivors is poorly evaluated. New biomarkers are needed to predict with higher accuracy the outcome of patients admitted with status in an intensive care unit. Here, we summarize the findings of studies from patients and animal models of status epilepticus. Specific protein markers can be detected in the cerebrospinal fluid and the blood. One of the first described markers of neuronal death is the neuron‐specific enolase. Gliosis resulting from inflammatory responses after status can be detected through the increase of S100‐beta, or some cytokines, like the High Mobility Group Box 1. Other proteins, like progranulin may reflect the neuroprotective mechanisms resulting from the brain adaptation to excitotoxicity. These new biomarkers aim to prospectively identify the severity and development of disability, and subsequent epilepsy of patients with status. We discuss the advantages and disadvantages of each biomarker, by evaluating their brain specificity, stability in the fluids, and sensitivity to external interferences, such as hemolysis. Finally, we emphasize the need for further development and validation of such biomarkers in order to better assess patients with severe status epilepticus.

show abstract

VEGF treatment during status epilepticus attenuates long-term seizure-associated alterations in astrocyte morphology

Cited by 14 publications

References 29 publications

Vascular Abnormalities and the Role of Vascular Endothelial Growth Factor in the Epileptic Brain

Vascular Abnormalities and the Role of Vascular Endothelial Growth Factor in the Epileptic Brain

Increase in Blood Levels of Growth Factors Involved in the Neuroplasticity Process by Using an Extremely Low Frequency Electromagnetic Field in Post-stroke Patients

Cerebrospinal fluid and blood biomarkers of status epilepticus

Contact Info

Product

Resources

About