Table 1.
Changes in function in experimental neonatal epilepsy models.
| References | Experimental epilepsy models | Animals | Brain regions | Changes |
|---|---|---|---|---|
| CONSISTENT WITH HIGH NKCC1 AND LOW KCC2 EXPRESSION | ||||
| In vivo | ||||
| Dzhala et al. (34) | KA-induced seizures | P9-12 rats | Hippocampus | Bumetanide attenuated electrographic seizure in neonatal rats. |
| Mares (70) | PTZ-induced seizures | P7,12,18 male albino rats of Wistar strain | – | Bumetanide only decreased tonic phase of P12 rats which showed higher NKCC1 expression than other periods. |
| Mazarati et al. (71) | Kindling-induced seizures | P11, P14, P21 Wistar rats |
Hippocampus | Bumetanide only increased ADT and shortened ADD in P11. Bumetanide delayed the occurrence, and reduced the number of full motor seizures. |
| Koyama et al. (67) | Hyperthermic seizure model |
P11 wildtype or transgenic SD male rats | Hippocampus | Bumetanide rescued granule cell ectopia and blocked increased susceptibility to adult seizures after febrile seizures at P11. |
| In vitro | ||||
| Dzhala et al. (34) | Bath application of high [K+]o |
P7-23 rats | Hippocampal slice |
Bumetanide suppressed and depressed IED, ID in P7-9 and P10-12 rats, respectively. |
| P7-9 NKCC1−/− mice | Hippocampal slice |
EGABA was more hyperpolarized and bumetanide did not change the amplitude and duration of IEDs. |
||
| Dzhala et al. (68) | Bath application continuous 5 h of low-Mg2+ solution |
P4-7 rats | Intact hippo- campal formations |
Bumetanide had a strong action in controlling ISIs and hyperpolarize EGABA. |
| Rheims et al. (72) | Bath application of 4-AP | P6-P9 rats | Neocortex slice | Bumetanide inhibited generation of IISs and prevented their trans- formation to ISs. |
| INCONSISTENT WITH HIGH NKCC1 AND LOW KCC2 EXPRESSION | ||||
| In vitro | ||||
| Kilb et al. (73) | High [K+]o model Disinhibition model Low-Mg2+ model Kainate model 4-AP/low-Mg2+ model |
P4-7 rats | Whole hippo- campus |
Bumetanide could attenuate epileptiform activity. Bumetanide had only little effect on interictal discharges. Bumetanide did not attenuate epileptiform activity but instead enhanced interictal activity. Bumetanide enhanced epileptiform activity. Bumetanide attenuated LRD like epileptiform activity. |
| Zhu et al. (74) | Bath application of 4-AP |
P9-P13 NKCC1+/+ and NKCC1−/− mice |
Hippocampaus | Bumetanide aggravated 4-AP induced seizures and enhanced neuronal excitability. |
| Nardou et al. (75) | Bath application of Kainate |
P7-8 Wistar rats | Interconnected intact hippo-campus |
Bumetanide did not prevent generation and propagation to the contralateral hippo-campal and the formation of an acute epileptogenic mirror focus. |
| Khirug et al. (76) | Kainate induced and bath application of kainate | P5-7 and P16 Wistar male rat pups | Hippocampus | Enhanced KCC2 function and a consequent negative shift in EGABA followed by seizure activity. |
| Awad et al. (77) | Freeze lesion and hyperthermic seizures |
P18-22 or P11-15 male rats |
Hippocampus | Amplitude of mEPSC in CA1 pyramidal neurons reduced significantly and EGABA increased which related to KCC2 over-expression. |
4-AP, 4-aminopyridine; ADT, after discharge threshold; ADD, after discharge duration; ID, ictal discharge; IED, interictal epileptic discharges; IISs, interictal seizures; ISs, ictal seizures; ISI, inter seizure intervals; KA, kainae; PTZ, pentylenetetrazol; mEPSC, miniature excitatory postsynaptic current; SD, Sprague-Dawley.