Summary:Mossy fiber sprouting is a major anatomical reorganization seen in patients with temporal lobe epilepsy and animal models of epilepsy. The final outcome of this reorganization is viewed by many as epileptogenic. Yet, important and relevant data from both human and animal models of epilepsy challenge this prevailing view. Regardless of the outcome of this debate, understanding of the mechanisms that underlie mossy fiber sprouting (MFS) might contribute to our understanding of both the adaptive and maladaptive changes that take place in the nervous system after injury. Available evidence suggests that two events might be crucial for mossy fibers to sprout in epilepsy: the death of mossy cells and the synthesis of trophic factors. The availability of means that prevent MFS, which is normally triggered after induction of status epilepticus, allow for the testing of hypotheses regarding the need for and the sufficiency of specific events for mossy fibers to sprout.We present data on a specific marker for mossy cells, calretinin, in the pilocarpine model of epilepsy in mice. Our data suggest that in the presence of a protein synthesis inhibitor status epilepticus-induced death of mossy cells is not sufficient to trigger mossy fiber sprouting. We suggest that both events, mossy cell death and synthesis of trophic factors, might be necessary for robust MFS to ensue. Key Words: Status epilepticus-Mossy fiber sprouting-Mossy cells-Dentate gyrus-Granule cells-GAP-43-Hippocampus-Temporal lobe epilepsy-Synaptic reorganization.It is becoming evident that temporal lobe epilepsy (TLE) is not a single pathological entity but rather might encompass many different pathologies and thus may be associated with various pathophysiologies. A good example of this plural side of the TLEs is the sprouting of the axons of granule cells onto the inner molecular layer (IML) of the dentate gyrus. These axons, the mossy fibers, which are not normally present in the IML of humans or of most other animals without epilepsy, might be conspicuously present in humans with TLE and animal models of epilepsy (1-5). Yet, it is clear that in some forms of TLE, there is little or no mossy fiber sprouting (MFS). According to a classification of TLE based on tissue analysis (6), both medial TLEs associated with mass lesions (tumors) and paradoxical medial TLEs might not present MFS.After the seminal demonstration of MFS in the IML in tissue from animal models of TLE (5), this form of synAddress correspondence and reprint requests to Dr. Luiz E. A. M. Mello at Department of Physiology, UNIFESP, Rua Botucatu 862, 04023-900 S2o Paulo, SP Brazil. E-mail: lemello@ecb.epm.br aptic reorganization has been demonstrated in almost every epileptic condition, even those not clearly associated with the temporal lobe (7). Despite the extensive demonstration of its presence in tissue from epilepsy patients and the clear theoretical background in favor of its role in epileptogenesis (8-1 7), the relevance of MFS to epileptic seizures remains a controversial issue. T...