Table 2.

Research and key findings on pericytes and epilepsy.

No.	Patients/Model	Species	Key Findings	Reference
1	Intractable complex partial seizures	Humans	Degeneration of pericytes (aggregates of cellular debris within the basement membrane) with the morphological changes in pericyte-basement membrane unit thickness and pericyte cytoplasmic density were observed in the spiking area of microvessels in an electron microscopy study of brain tissue	[63]
2	TLE with HS	Humans	PDGFRβ+ cells are distributed around the cerebrovasculature and are present in the brain parenchyma of human TLE specimens	[2]
	NG2DsRed or C57BL/6J mice (intraperitoneal KA injections)	Mice	Constitutive cerebrovascular NG2DsRed pericyte coverage is impaired in response to SE in vivo or seizure-like events in vitro Redistribution of parenchymal and vascular PDGFRβ+ cells occurs in vitro and in vivo Vascular and parenchymal PDGFRβ+ cells partially co-localize with NG2DsRed and NG2, but not with IBA-1 (indicators of microglia)
3	FCD, TLE without HS, cryptogenic epilepsy	Humans	FCD and TLE-HS display the highest PDGFRβ immunoreactivity at the microvasculature identifying pericytes Cryptogenic epilepsy patients also showed a similar immune response pattern, although to a lesser extent than that in FCD The amount of perivascular PDGFRβ immunoreactivity was found to be associated with increased hippocampal angiogenesis in tissues from patients with TLE-HS	[25]
	Neurovascular dysplasia rat model (Sprague-Dawley rats with pre-natal exposure to methyl-axozy methanoic acid), pilocarpine	Mice	Pericyte-vascular dysplasia was detected in hippocampi corresponding to neuronal heterotopias Severe SE was associated with a region-specific increase in PDGFRβ immunoreactivity
4	TLE	Humans	Chronic IFN-γ treatment blocks signaling through PDGFRβ by enhancing agonist PDGF-BB	[26]
5	Drug-resistant TLE (microarray analysis)	human	TGFβ1 decreased pericyte proliferation and decreased phagocytosis TGFβ1 also upregulates the expression of IL-6, MMP-2, and NOX4, which disrupt the function of the BBB, and these responses to TGFβ1 may not be therapeutic for the neurovascular system	[27]
6	Dynamics of NG2 mural cells under SE with systemic KA injection in mice	Mice	NG2 mural cells are added and removed from veins, arterioles, and capillaries after status epilepticus Loss of NG2 mural cells is proportional to seizure severity and vascular pathology (e.g., rigidity, perfusion, and permeability) Treatment with PDGF-BB reduced NG2 mural cell loss, vascular pathology, and epileptiform electroencephalogram activity	[28]
7	TLE with or without HS, FCD	Humans	Pericyte-microglia assemblies with IBA1/HLA microglial cells outlining the capillary wall were observed in TLE-HS and FCD-IIb specimens Proinflammatory cytokines such as IL-1β cause morphological changes and IL-6 causes cell damage in human-derived pericytes	[29]
	NG2DsRed/C57BL6 (unilateral intra-hippocampal KA injections)	Mice	IL-1β elicited pericyte morphological changes and pericyte-microglia clustering in NG2DsRed hippocampal slices
8	NG2DsRed/C57BL6 (unilateral intra-hippocampal KA injections)	Mice	Multicellular scarring occurs at the outer capillary wall in the hippocampus during seizure progression PDGFRβ stromal cells and collagens III and IV participate in the localized pericyte-glial scarring and capillary pathology in hippocampal subregions PDGFRβ is a proposed anti-inflammatory entry point for chronic disease stages in vivo	[30]
9	Transgenic mice (4-aminopyridine or low-Mg2+ conditions)	Mice	Pericytes regulate changes in vascular diameter in response to neuronal activity Recurrent seizures are associated with impaired neurovascular coupling and increased BBB permeability in capillaries Recurrent seizures lead to depolarization of pericytic mitochondria and subsequent vasoconstriction	[31]
10	Traumatic brain injury model (C57BL/6J mice with CCI and pilocarpine injections)	Mice	PDGFRβ levels were increased from 1 h to 4 days after CCI in the injured ipsilateral hippocampus prior to increased expression of markers of microglia and astrocytes; this supports the postulated role of pericytes as initiators of the CNS immune response Treatment with imatinib on postoperative days 0–4 reduced seizure susceptibility, demonstrating the usefulness of imatinib in vitro	[32]

CCI, controlled cortical impact; FCD, focal cortical dysplasia, HS, hippocampal sclerosis; IP, intraperitoneal; KA, kainic acid; PDGF-BB, platelet-derived growth factor-beta subunit; SE, status epilepticus; TBI, traumatic brain injury; TLE, temporal lobe epilepsy.