Antiepileptic and neuroprotective effects of human umbilical cord blood mononuclear cells in a pilocarpine-induced epilepsy model

Abstract

Status epilepticus (SE) is a condition of persistent seizure that leads to brain damage and, frequently, to the establishment of chronic epilepsy. Cord blood is an important source of adult stem cells for the treatment of neurological disorders. The present study aimed to evaluate the effects of human umbilical cord blood mononuclear cells (HUCBC) transplanted into rats after induction of SE by the administration of lithium and pilocarpine chloride. Transplantation of HUCBC into epileptic rats protected against neuronal loss in the hippocampal subfields CA1, CA3 and in the hilus of the dentate gyrus, up to 300 days after SE induction. Moreover, transplanted rats had reduced frequency and duration of spontaneous recurrent seizures (SRS) 15, 120 and 300 days after the SE. Our study shows that HUCBC provide prominent antiepileptic and neuroprotective effects in the experimental model of epilepsy and reinforces that early interventions can protect the brain against the establishment of epilepsy.

Concise Review: Prospects of Bone Marrow Mononuclear Cells and Mesenchymal Stem Cells for Treating Status Epilepticus and Chronic Epilepsy

“…Additionally, since BM‐MNC cell suspension is a mixture of B‐lymphocytes, T‐lymphocytes, monocytes in different stages of maturation, and progenitors such as hematopoietic stem cells, MSCs, endothelial progenitor cells, and very small embryonic‐like cells , it was unclear whether the beneficial effects observed were due to all BM‐MNCs or other specialized progenitors such as MSCs. Another study using a rat model of SE showed that administration of MNCs from the human umbilical cord is also efficacious for providing hippocampus neuroprotection and reducing SRS in the chronic phase of epilepsy . Collectively, these results imply that administration of MNCs early after SE is efficacious for restraining chronic epilepsy development, regardless of the source from which MNCs are derived.…”

“…Moreover, it is imperative to identify the best route for administration of MNCs or MSCs for epileptic conditions. Animal model studies in epilepsy have so far used intravenous, intracerebral, or intraperitoneal routes of administration and have shown some efficacy with all of these approaches . Nonetheless, exploring the efficacy of additional routes may be important, since studies in other neurological models have shown that administration of these cells through intranasal routes are also efficacious.…”

Neural stem cells: ready for therapeutic applications?

“…Antiepileptic and neuroprotective effects have also been reported after transplantation of different types of stem cells. Grafting of human umbilical cord stem cells [ 53 ] or genetically-engineered bone marrow mesenchymal stem cells [ 54 ] have been shown to ameliorate seizures in the pilocarpine rat model of TLE.…”

Could Cord Blood Cell Therapy Reduce Preterm Brain Injury?

“…Transplantation of hUCB–MNCs 90 min after the onset of status epilepticus in rats, induced by lithium and pilocarpine chloride, protected against neuronal loss in the hippocampus for up to 300 days. Additionally, MNC-transplanted rats had reduced frequency and duration of recurrent seizures, suggesting early administration could protect against the establishment of epilepsy ( 161 ). Furthermore in a single case of an infant with infantile spasms (West syndrome) and X-linked T/B + NK-severe combined immunodeficiency, allogeneic UCB transplantation together with topiramate and immune-modulating agents (corticosteroids, intravenous immunoglobulin, and tacrolimus) improved seizures, possibly contributed by an immuno-modulatory effect of UCB–MNCs ( 162 ).…”