Table 1.
Early Intervention or Prophylactic Studies of Primary GABA-ergic Cell Grafts in Epilepsy Models (2008-present)
| Animal Prototype and Type of Donor Cells |
Timing and Site of Grafting |
Time-point of Seizure Analyses & Effects on Seizures |
Effects on Memory/M ood Function |
Graft Cell Survival, Differentiation and Integration |
Effects of Grafts on Epileptogenic Changes in the Host Brain |
|---|---|---|---|---|---|
| Kainate induced SE in rats Gamma-amino butyric acid positive (GABA- ergic) progenitors from the embryonic day 15 (E15) rat lateral ganglionic eminence (LGE) treated with fibroblast growth factor-2 Hattiangady et al., 2008 |
4 days after status epilepticus (SE) Grafts placed into the Hippocampus |
9–12 months after grafting 67–89% decrease in the frequency spontaneous recurrent seizures (SRS) |
Not Assessed |
Recovery equivalent to 33% of injected cells (at one year post-grafting) Differentiated into neurons expressing GABA (69%), neuropeptide Y (NPY, 8%), parvalbumin (PV, 29%), calbindin (CBN, 30%) & calretinin (CR, 31%) |
Enhanced CBN expression in dentate granule cells No effects on aberrant mossy fiber sprouting |
| Shaker-like potassium channel (Kv1.1/Kcna1) mutant mouse GABA-ergic progenitors from the E13.5 mouse medial ganglionic eminence (MGE) Baraban et al., 2009 |
Postnatal Day 2 Grafts placed into the neocortex |
2nd month after grafting Significant reductions in the duration and frequency of spontaneous electrographic seizures |
Not Assessed |
Survival: % not reported. Differentiated into neurons expressing GABA (65%), PV (29%), somatostatin (SST, 44%), NPY (10%) & CR (5%) |
Not Examined |
| Mouse model of seizure vulnerability induced by an injection of SSP- Sap (a conjugate of peptidase-resistant [Sar9, Met(O2)11] analog of substance P and the ribosome-inactivating protein saporin) GABA-ergic progenitors from the E12.5 mouse MGE Zipancic et al., 2010 |
1-week after injection of SSP-Sap Grafts placed into the Hippocampus |
2-months after SSP-Sap injection Significantly decreased sensitivity and diminished mortality to pentylenetetra zol (PTZ) induced seizures |
Not Assessed |
Survival: 18–20% at 2–12 months post- grafting Differentiated into neurons expressing GABA (65%), PV (35%), SST (34%), NPY (19%), neurokinin-1 (NK-1, 26%) & CR (4%) |
Grafting normalized inhibitory postsynaptic current (IPSC) frequency and amplitude in the CA1 pyramidal neurons |
| A mouse model of maximum electroconvulsive shock (MES) GABA-ergic progenitors from the mouse embryonic MGE Calcagnotto et al., 2010 |
Neonatal mice Grafts placed into the cortex |
Two months after grafting, mice were submitted to MES Grafting altered the course of MES acute seizures, increased seizure threshold, and/or blocked the generalized convulsive activity |
Not Assessed |
Survival: % not reported Qualitative assessment showed graft-derived cells expressing GABA, NPY, CR and PV. Grafted cells migrated into the surrounding brain regions |
Not Examined |
| A rat model of kindling epilepsy GABA-ergic progenitors from the E14.5 rat MGE Gallego et al., 2010 |
3-days after full kindling Grafts placed into the amygdala |
At 3–24 days after grafting Increased after discharge and seizure thresholds |
Not Assessed |
Survival: qualitative assessment showed GABA+ cells |
Not Examined |
| A mouse model of 4- aminopyridine (4-AP) induced acute epileptiform discharges in the neocortex GABA-ergic progenitors from the mouse E13.5 MGE De la Cruz et al., 2011 |
6–8 week old mice Grafts placed into the sensorimotor cortex |
Injection of 4- AP ~2mm away from grafts at 2–8 weeks post- grafting A dramatic reduction in local field potential power at the MGE transplanted area |
Not Assessed |
Survival: Exact percentage not reported. Semi- quantitative assessment suggested lower yield Graft-derived cells differentiated into neurons expressing GABA (54–57%), SST (38–40%) and PV (13–17%) |
Reduction in ictal power did not correlate with graft cell number, implying the presence of a non-synpatic mechanism |