RARE DISEASE
Cerebral diseases of vascular origin with epilepsy
Cerebral diseases of vascular origin with epilepsy
Cerebral diseases of vascular origin with epilepsy
Drug discovery
8
papers
On emerging therapies
Overview
Cerebrovascular diseases, including ischemic stroke, hemorrhagic stroke, and small vessel disease, are leading causes of epilepsy, particularly in older adults. Vascular insults disrupt cerebral blood flow, triggering acute symptomatic seizures (within 7 days of injury) or late-onset epilepsy (delayed seizures). Cortical involvement, hemorrhagic transformation, and comorbidities like hypertension increase seizure risk. Post-stroke epilepsy is linked to higher morbidity, mortality, and reduced quality of life [4][8][11][15].
Burden
Contributes to ~28 million global epilepsy cases (secondary etiology) [3][7].
Associated with 2–3× higher mortality vs. general epilepsy, often due to cardiovascular complications [11][15].
Economic burden includes prolonged hospitalization, increased disability-adjusted life years (DALYs), and higher healthcare costs [3][13].
Therapies
Antiseizure medications (ASMs): First-line for seizure control; levetiracetam and valproic acid are commonly used [14][18].
Neurostimulation: Vagal nerve stimulation (VNS) or deep brain stimulation (DBS) for drug-resistant cases [6][8].
Vascular risk management: Aggressive control of hypertension and diabetes to mitigate secondary epileptogenesis [4][11].
Categories: rare genetic diseases, rare neurological diseases
Research Papers
8 drug discovery papers about Cerebral diseases of vascular origin with epilepsy. Recent publications:
8 drug discovery papers about Cerebral diseases of vascular origin with epilepsy. Recent publications:
categories:
Small molecules
small molecules
2026-06-12 | Glymphatic-meningeal lymphatic dysfunction in epilepsy: novel mechanistic insights and therapeutic avenues.
Despite advances in pharmacotherapy, approximately one-third of individuals with epilepsy develop drug-resistant epilepsy (DRE), accounting for a disproportionate share of the global disease burden. Emerging evidence implicates dysfunction of the meningeal lymphatic system-a critical regulator of waste clearance and immune surveillance-in the pathogenesis of DRE. This suggests that impaired lymphatic drainage may represent a novel mechanistic pathway and therapeutic target. In this review, we systematically examine the interplay between the lymphatic drainage and neural networks in epileptogenesis. We map the neuroimmunological landscape, delineate the crosstalk between peripheral immune cells and resident glia in the central nervous system (CNS), and evaluate how blood-brain barrier disruption contributes to seizure progression. Central to our synthesis is the "lymphatic drainage-neural network" paradigm, through which we characterize dynamic alterations in the glymphatic system (GS) and meningeal lymphatic vessels (mLVs) across ictal and interictal states. We further explore how these systems drive epilepsy-associated comorbidities and assess emerging therapeutic strategies aimed at restoring lymphatic function. We conclude by highlighting the critical role of the meningeal lymphatic system, particularly the GS, in fostering epileptogenesis. While direct experimental evidence linking mLVs to epilepsy remains nascent, their established contribution of impaired immune surveillance and dysfunctional cerebral lymphatic drainage to diverse CNS disorders strongly positions mLVs-alongside the GS-as compelling therapeutic targets. We advocate for intensified investigation into the lymphatic drainage system as an active and indispensable frontier in epilepsy research.
2010-06-23 | Epileptic seizures increase circulating endothelial cells in peripheral blood as early indicators of cerebral vascular damage.
Circulating endothelial cells (CECs) are nonhematopoetic mononuclear cells in peripheral blood that are dislodged from injured vessels during cardiovascular disease, systemic vascular disease, and inflammation. Their occurrence during cerebrovascular insults has not been previously described. Epileptic seizures cause the long-term loss of cerebrovascular endothelial dilator function. We hypothesized that seizures cause endothelial sloughing from cerebral vessels and the appearance of brain-derived CECs (BCECs), possible early indicators of cerebral vascular damage. Epileptic seizures were induced by bicuculline in newborn pigs; venous blood was then sampled during a 4-h period. CECs were identified in the fraction of peripheral blood mononuclear cells by the expression of endothelial antigens (CD146, CD31, and endothelial nitric oxide synthase) and by Ulex europeaus lectin binding. In control animals, few CECs were detected. Seizures caused a time-dependent increase in CECs 2-4 h after seizure onset. Seizure-induced CECs coexpress glucose transporter-1, a blood-brain barrier-specific glucose transporter, indicating that these cells originate in the brain vasculature and are thus BCECs. Seizure-induced BCECs cultured in EC media exhibited low proliferative potential and abnormal cell contacts. BCEC appearance during seizures was blocked by a CO-releasing molecule (CORM-A1) or cobalt protoporphyrin (heme oxygenase-1 inducer), which prevented apoptosis in cerebral arterioles and the loss of cerebral vascular endothelial function during the late postictal period. These findings suggest that seizure-induced BCECs are injured ECs dislodged from cerebral microvessels during seizures. The correlation between the appearance of BCECs in peripheral blood, apoptosis in cerebral vessels, and the loss of postictal cerebral vascular function suggests that BCECs are early indicators of late cerebral vascular damage.
2009-04-09 | Comparison of acute, chronic and post-treatment effects of carbamazepine and vinpocetine on hearing loss and seizures induced by 4-aminopyridine.
To compare the acute, chronic and post-treatment effects of the classic antiepileptic drug carbamazepine (CBZ) and the potential antiepileptic vinpocetine (VPC), successfully used in the treatment of brain vascular origin disorders, on 4-aminopyridine (4-AP)-induced increase in auditory threshold, brain-auditory-evoked-potentials (BAEPs) later waves alterations and epileptiform activity. BAEP and EEG recordings before and following 4-AP (3mg/kg, i.p.) were obtained in guinea pigs. One week after, the animals received a daily injection (i.p.) of vehicle, 3mg/kg VPC or 17 mg/kg CBZ for 13 days. The acute and chronic effects before and following 4-AP were tested at the 1st and last days, respectively, and the post-treatment effect 1 month after the end of treatment. CBZ and 4-AP increased BAEPs threshold and BAEPs P4 wave latency. Chronic CBZ inhibited 4-AP-induced increase in P3 amplitude. In the VPC-treated group, all the 4-AP-induced BAEPs changes were prevented. Seizures were prevented in 50% and 75% of the animals by chronic CBZ and VPC, respectively. After acute VPC and after the end of VPC-treatment 4-AP failed to induce seizures in 50% of the animals. VPC inhibits 4-AP-induced seizures and hearing loss, even after post-treatment, at a concentration about 10 times lower than CBZ. The complications in hearing that can accompany epilepsy can be prevented by VPC, indicating its advantage as an alternative antiepileptic.
1981-04-21 | Temporal lobe epilepsy and hemianopsia in childhood of perinatal origin. An overlooked and potentially treatable disease? Report of two cases, one with a demonstrable etiology.
Two children with a history of traumatic delivery developed severe temporal lobe epilepsy starting at age 4 and 10 respectively. The main neurological finding was total homonymous hemianopsia. The CAT Scan showed a large localised hypodensity in the occipital region on one side consistent with an old infarction in that region. A similar clinical syndrome was described in 1974 by Remillard as temporal lobe epilepsy and perinatal occlusion of the posterior cerebral artery (PCA). In one of our cases, the clinical course suggested that vascular occlusion in the PCA territory resulted from temporal lobe herniation related to a subdural hematoma at birth. It is proposed that this mechanism may apply to some instances of that condition. This clinical syndrome is now increasingly diagnosed as a large number of epileptics are now submitted to CAT. The diagnosis can be delayed until a seizure disorder develops because of the frequent absence of obvious neuromotor signs or visual complaints in the first years of life. Early recognition of this particular type of neonatal cerebral injury could possibly lead to prevention or early treatment.
cell therapies
2023-10-03 | Interneuron odyssey: molecular mechanisms of tangential migration.
Cortical GABAergic interneurons are critical components of neural networks. They provide local and long-range inhibition and help coordinate network activities involved in various brain functions, including signal processing, learning, memory and adaptative responses. Disruption of cortical GABAergic interneuron migration thus induces profound deficits in neural network organization and function, and results in a variety of neurodevelopmental and neuropsychiatric disorders including epilepsy, intellectual disability, autism spectrum disorders and schizophrenia. It is thus of paramount importance to elucidate the specific mechanisms that govern the migration of interneurons to clarify some of the underlying disease mechanisms. GABAergic interneurons destined to populate the cortex arise from multipotent ventral progenitor cells located in the ganglionic eminences and pre-optic area. Post-mitotic interneurons exit their place of origin in the ventral forebrain and migrate dorsally using defined migratory streams to reach the cortical plate, which they enter through radial migration before dispersing to settle in their final laminar allocation. While migrating, cortical interneurons constantly change their morphology through the dynamic remodeling of actomyosin and microtubule cytoskeleton as they detect and integrate extracellular guidance cues generated by neuronal and non-neuronal sources distributed along their migratory routes. These processes ensure proper distribution of GABAergic interneurons across cortical areas and lamina, supporting the development of adequate network connectivity and brain function. This short review summarizes current knowledge on the cellular and molecular mechanisms controlling cortical GABAergic interneuron migration, with a focus on tangential migration, and addresses potential avenues for cell-based interneuron progenitor transplants in the treatment of neurodevelopmental disorders and epilepsy.
2019-11-08 | In vitro 3D regeneration-like growth of human patient brain tissue.
In vitro culture of primary neurons is widely adapted with embryonic but not mature brain tissue. Here, we extended a previously developed bioengineered three-dimensional (3D) embryonic brain tissue model to resected normal patient brain tissue in an attempt to regenerate human neurons in vitro. Single cells and small sized (diameter < 100 μm) spheroids from dissociated brain tissue were seeded into 3D silk fibroin-based scaffolds, with or without collagen or Matrigel, and compared with two-dimensional cultures and scaffold-free suspension cultures. Changes of cell phenotypes (neuronal, astroglial, neural progenitor, and neuroepithelial) were quantified with flow cytometry and analyzed with a new method of statistical analysis specifically designed for percentage comparison. Compared with a complete lack of viable cells in conventional neuronal cell culture condition, supplements of vascular endothelial growth factor-containing pro-endothelial cell condition led to regenerative growth of neurons and astroglial cells from "normal" human brain tissue of epilepsy surgical patients. This process involved delayed expansion of Nestin+ neural progenitor cells, emergence of TUJ1+ immature neurons, and Vimentin+ neuroepithelium-like cell sheet formation in prolonged cultures (14 weeks). Micro-tissue spheroids, but not single cells, supported the brain tissue growth, suggesting importance of preserving native cell-cell interactions. The presence of 3D scaffold, but not hydrogel, allowed for Vimentin+ cell expansion, indicating a different growth mechanism than pluripotent cell-based brain organoid formation. The slow and delayed process implied an origin of quiescent neural precursors in the neocortex tissue. Further optimization of the 3D tissue model with primary human brain cells could provide personalized brain disease models.
small molecules
2026-06-12 | Glymphatic-meningeal lymphatic dysfunction in epilepsy: novel mechanistic insights and therapeutic avenues.
Despite advances in pharmacotherapy, approximately one-third of individuals with epilepsy develop drug-resistant epilepsy (DRE), accounting for a disproportionate share of the global disease burden. Emerging evidence implicates dysfunction of the meningeal lymphatic system-a critical regulator of waste clearance and immune surveillance-in the pathogenesis of DRE. This suggests that impaired lymphatic drainage may represent a novel mechanistic pathway and therapeutic target. In this review, we systematically examine the interplay between the lymphatic drainage and neural networks in epileptogenesis. We map the neuroimmunological landscape, delineate the crosstalk between peripheral immune cells and resident glia in the central nervous system (CNS), and evaluate how blood-brain barrier disruption contributes to seizure progression. Central to our synthesis is the "lymphatic drainage-neural network" paradigm, through which we characterize dynamic alterations in the glymphatic system (GS) and meningeal lymphatic vessels (mLVs) across ictal and interictal states. We further explore how these systems drive epilepsy-associated comorbidities and assess emerging therapeutic strategies aimed at restoring lymphatic function. We conclude by highlighting the critical role of the meningeal lymphatic system, particularly the GS, in fostering epileptogenesis. While direct experimental evidence linking mLVs to epilepsy remains nascent, their established contribution of impaired immune surveillance and dysfunctional cerebral lymphatic drainage to diverse CNS disorders strongly positions mLVs-alongside the GS-as compelling therapeutic targets. We advocate for intensified investigation into the lymphatic drainage system as an active and indispensable frontier in epilepsy research.
2010-06-23 | Epileptic seizures increase circulating endothelial cells in peripheral blood as early indicators of cerebral vascular damage.
Circulating endothelial cells (CECs) are nonhematopoetic mononuclear cells in peripheral blood that are dislodged from injured vessels during cardiovascular disease, systemic vascular disease, and inflammation. Their occurrence during cerebrovascular insults has not been previously described. Epileptic seizures cause the long-term loss of cerebrovascular endothelial dilator function. We hypothesized that seizures cause endothelial sloughing from cerebral vessels and the appearance of brain-derived CECs (BCECs), possible early indicators of cerebral vascular damage. Epileptic seizures were induced by bicuculline in newborn pigs; venous blood was then sampled during a 4-h period. CECs were identified in the fraction of peripheral blood mononuclear cells by the expression of endothelial antigens (CD146, CD31, and endothelial nitric oxide synthase) and by Ulex europeaus lectin binding. In control animals, few CECs were detected. Seizures caused a time-dependent increase in CECs 2-4 h after seizure onset. Seizure-induced CECs coexpress glucose transporter-1, a blood-brain barrier-specific glucose transporter, indicating that these cells originate in the brain vasculature and are thus BCECs. Seizure-induced BCECs cultured in EC media exhibited low proliferative potential and abnormal cell contacts. BCEC appearance during seizures was blocked by a CO-releasing molecule (CORM-A1) or cobalt protoporphyrin (heme oxygenase-1 inducer), which prevented apoptosis in cerebral arterioles and the loss of cerebral vascular endothelial function during the late postictal period. These findings suggest that seizure-induced BCECs are injured ECs dislodged from cerebral microvessels during seizures. The correlation between the appearance of BCECs in peripheral blood, apoptosis in cerebral vessels, and the loss of postictal cerebral vascular function suggests that BCECs are early indicators of late cerebral vascular damage.
2009-04-09 | Comparison of acute, chronic and post-treatment effects of carbamazepine and vinpocetine on hearing loss and seizures induced by 4-aminopyridine.
To compare the acute, chronic and post-treatment effects of the classic antiepileptic drug carbamazepine (CBZ) and the potential antiepileptic vinpocetine (VPC), successfully used in the treatment of brain vascular origin disorders, on 4-aminopyridine (4-AP)-induced increase in auditory threshold, brain-auditory-evoked-potentials (BAEPs) later waves alterations and epileptiform activity. BAEP and EEG recordings before and following 4-AP (3mg/kg, i.p.) were obtained in guinea pigs. One week after, the animals received a daily injection (i.p.) of vehicle, 3mg/kg VPC or 17 mg/kg CBZ for 13 days. The acute and chronic effects before and following 4-AP were tested at the 1st and last days, respectively, and the post-treatment effect 1 month after the end of treatment. CBZ and 4-AP increased BAEPs threshold and BAEPs P4 wave latency. Chronic CBZ inhibited 4-AP-induced increase in P3 amplitude. In the VPC-treated group, all the 4-AP-induced BAEPs changes were prevented. Seizures were prevented in 50% and 75% of the animals by chronic CBZ and VPC, respectively. After acute VPC and after the end of VPC-treatment 4-AP failed to induce seizures in 50% of the animals. VPC inhibits 4-AP-induced seizures and hearing loss, even after post-treatment, at a concentration about 10 times lower than CBZ. The complications in hearing that can accompany epilepsy can be prevented by VPC, indicating its advantage as an alternative antiepileptic.
1981-04-21 | Temporal lobe epilepsy and hemianopsia in childhood of perinatal origin. An overlooked and potentially treatable disease? Report of two cases, one with a demonstrable etiology.
Two children with a history of traumatic delivery developed severe temporal lobe epilepsy starting at age 4 and 10 respectively. The main neurological finding was total homonymous hemianopsia. The CAT Scan showed a large localised hypodensity in the occipital region on one side consistent with an old infarction in that region. A similar clinical syndrome was described in 1974 by Remillard as temporal lobe epilepsy and perinatal occlusion of the posterior cerebral artery (PCA). In one of our cases, the clinical course suggested that vascular occlusion in the PCA territory resulted from temporal lobe herniation related to a subdural hematoma at birth. It is proposed that this mechanism may apply to some instances of that condition. This clinical syndrome is now increasingly diagnosed as a large number of epileptics are now submitted to CAT. The diagnosis can be delayed until a seizure disorder develops because of the frequent absence of obvious neuromotor signs or visual complaints in the first years of life. Early recognition of this particular type of neonatal cerebral injury could possibly lead to prevention or early treatment.
cell therapies
2023-10-03 | Interneuron odyssey: molecular mechanisms of tangential migration.
Cortical GABAergic interneurons are critical components of neural networks. They provide local and long-range inhibition and help coordinate network activities involved in various brain functions, including signal processing, learning, memory and adaptative responses. Disruption of cortical GABAergic interneuron migration thus induces profound deficits in neural network organization and function, and results in a variety of neurodevelopmental and neuropsychiatric disorders including epilepsy, intellectual disability, autism spectrum disorders and schizophrenia. It is thus of paramount importance to elucidate the specific mechanisms that govern the migration of interneurons to clarify some of the underlying disease mechanisms. GABAergic interneurons destined to populate the cortex arise from multipotent ventral progenitor cells located in the ganglionic eminences and pre-optic area. Post-mitotic interneurons exit their place of origin in the ventral forebrain and migrate dorsally using defined migratory streams to reach the cortical plate, which they enter through radial migration before dispersing to settle in their final laminar allocation. While migrating, cortical interneurons constantly change their morphology through the dynamic remodeling of actomyosin and microtubule cytoskeleton as they detect and integrate extracellular guidance cues generated by neuronal and non-neuronal sources distributed along their migratory routes. These processes ensure proper distribution of GABAergic interneurons across cortical areas and lamina, supporting the development of adequate network connectivity and brain function. This short review summarizes current knowledge on the cellular and molecular mechanisms controlling cortical GABAergic interneuron migration, with a focus on tangential migration, and addresses potential avenues for cell-based interneuron progenitor transplants in the treatment of neurodevelopmental disorders and epilepsy.
2019-11-08 | In vitro 3D regeneration-like growth of human patient brain tissue.
In vitro culture of primary neurons is widely adapted with embryonic but not mature brain tissue. Here, we extended a previously developed bioengineered three-dimensional (3D) embryonic brain tissue model to resected normal patient brain tissue in an attempt to regenerate human neurons in vitro. Single cells and small sized (diameter < 100 μm) spheroids from dissociated brain tissue were seeded into 3D silk fibroin-based scaffolds, with or without collagen or Matrigel, and compared with two-dimensional cultures and scaffold-free suspension cultures. Changes of cell phenotypes (neuronal, astroglial, neural progenitor, and neuroepithelial) were quantified with flow cytometry and analyzed with a new method of statistical analysis specifically designed for percentage comparison. Compared with a complete lack of viable cells in conventional neuronal cell culture condition, supplements of vascular endothelial growth factor-containing pro-endothelial cell condition led to regenerative growth of neurons and astroglial cells from "normal" human brain tissue of epilepsy surgical patients. This process involved delayed expansion of Nestin+ neural progenitor cells, emergence of TUJ1+ immature neurons, and Vimentin+ neuroepithelium-like cell sheet formation in prolonged cultures (14 weeks). Micro-tissue spheroids, but not single cells, supported the brain tissue growth, suggesting importance of preserving native cell-cell interactions. The presence of 3D scaffold, but not hydrogel, allowed for Vimentin+ cell expansion, indicating a different growth mechanism than pluripotent cell-based brain organoid formation. The slow and delayed process implied an origin of quiescent neural precursors in the neocortex tissue. Further optimization of the 3D tissue model with primary human brain cells could provide personalized brain disease models.
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