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Perirhinal cortex and temporal lobe epilepsy.

Biagini G, D'Antuono M, Benini R, de Guzman P, Longo D, Avoli M - Front Cell Neurosci (2013)

Bottom Line: The perirhinal cortex-which is interconnected with several limbic structures and is intimately involved in learning and memory-plays major roles in pathological processes such as the kindling phenomenon of epileptogenesis and the spread of limbic seizures.However, we have recently identified in pilocarpine-treated epileptic rats the presence of selective losses of interneuron subtypes along with increased synaptic excitability.Overall, these data indicate that perirhinal cortex networks are hyperexcitable in an animal model of temporal lobe epilepsy, and that this condition is associated with a selective cellular damage that is characterized by an age-dependent sensitivity of interneurons to precipitating injuries, such as status epilepticus.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Experimental Epileptology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia Modena, Italy.

ABSTRACT
The perirhinal cortex-which is interconnected with several limbic structures and is intimately involved in learning and memory-plays major roles in pathological processes such as the kindling phenomenon of epileptogenesis and the spread of limbic seizures. Both features may be relevant to the pathophysiology of mesial temporal lobe epilepsy that represents the most refractory adult form of epilepsy with up to 30% of patients not achieving adequate seizure control. Compared to other limbic structures such as the hippocampus or the entorhinal cortex, the perirhinal area remains understudied and, in particular, detailed information on its dysfunctional characteristics remains scarce; this lack of information may be due to the fact that the perirhinal cortex is not grossly damaged in mesial temporal lobe epilepsy and in models mimicking this epileptic disorder. However, we have recently identified in pilocarpine-treated epileptic rats the presence of selective losses of interneuron subtypes along with increased synaptic excitability. In this review we: (i) highlight the fundamental electrophysiological properties of perirhinal cortex neurons; (ii) briefly stress the mechanisms underlying epileptiform synchronization in perirhinal cortex networks following epileptogenic pharmacological manipulations; and (iii) focus on the changes in neuronal excitability and cytoarchitecture of the perirhinal cortex occurring in the pilocarpine model of mesial temporal lobe epilepsy. Overall, these data indicate that perirhinal cortex networks are hyperexcitable in an animal model of temporal lobe epilepsy, and that this condition is associated with a selective cellular damage that is characterized by an age-dependent sensitivity of interneurons to precipitating injuries, such as status epilepticus.

No MeSH data available.


Related in: MedlinePlus

Cholecystokinin (CCK)-immunopositive interneurons in the rat perirhinal cortex. Photomicrographs showing interneurons stained with an antibody against CCK in the perirhinal cortex of 3-week-old rats (A–C). Specifically, CCK immunostaining in a control, non-epileptic rat, (A) and in pilocarpine-treated rats 3 (B) and 14 days (C) after pilocarpine treatment are respectively shown. (D) Normalized (respect to control) quantification of CCK immunostained neurons in 3 and 8-week-old rats following pilocarpine treatment. Note in the 3-week-old animals (n = 3–6 for each time interval) that CCK immunostained neurons decrease significantly 3 days after pilocarpine but recovered 7 and 14 days later. Note also that a consistent decrease in CCK-positive neurons was observed in 8-week-old rats (n = 4–5 for each time interval). **p < 0.01, analysis of variance followed by Tukey's test for multiple comparisons. Scale bar: 100 μm. Animal treatment is described in Biagini et al. (2008). Details of the immunostaining procedure and cell counts are as in Benini et al. (2011) and Gualtieri et al. (2013).
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Figure 7: Cholecystokinin (CCK)-immunopositive interneurons in the rat perirhinal cortex. Photomicrographs showing interneurons stained with an antibody against CCK in the perirhinal cortex of 3-week-old rats (A–C). Specifically, CCK immunostaining in a control, non-epileptic rat, (A) and in pilocarpine-treated rats 3 (B) and 14 days (C) after pilocarpine treatment are respectively shown. (D) Normalized (respect to control) quantification of CCK immunostained neurons in 3 and 8-week-old rats following pilocarpine treatment. Note in the 3-week-old animals (n = 3–6 for each time interval) that CCK immunostained neurons decrease significantly 3 days after pilocarpine but recovered 7 and 14 days later. Note also that a consistent decrease in CCK-positive neurons was observed in 8-week-old rats (n = 4–5 for each time interval). **p < 0.01, analysis of variance followed by Tukey's test for multiple comparisons. Scale bar: 100 μm. Animal treatment is described in Biagini et al. (2008). Details of the immunostaining procedure and cell counts are as in Benini et al. (2011) and Gualtieri et al. (2013).

Mentions: At variance with PV-immunopositive cells, CCK interneurons in the perirhinal cortex showed transitory changes in 3-week-old rats. This phenomenon, which may reflect functional adaptation to status epilepticus rather than cell damage, was limited to young rats whereas adult rats presented merely with loss of interneurons. As shown in Figures 7A–D, interneurons stained by an antibody against CCK (Benini et al., 2011; Gualtieri et al., 2013) were significantly (p < 0.01) reduced in 3-week-old rats at day 3 after pilocarpine treatment, but counts of these interneurons were comparable to control values at days 7 and 14 after status epilepticus. This finding could be related to a transient impairment in CCK synthesis or to an increased release. In contrast with the time course observed in the young group of animals, 8-week-old rats presented a strong reduction in CCK immunopositive cells to ~ 20% of control values, which was found at every considered time point (Figure 7D). Interestingly, these results highlight a different age-related sensitivity of CCK interneurons to pilocarpine-induced status epilepticus by confirming an enhanced resilience to damage in young animals. It remains to be established, however, whether this difference could be related to the lower propensity of young rats to develop recurrent generalized seizures when exposed to status epilepticus, in contrast to what observed in adult animals (Biagini et al., 2008).


Perirhinal cortex and temporal lobe epilepsy.

Biagini G, D'Antuono M, Benini R, de Guzman P, Longo D, Avoli M - Front Cell Neurosci (2013)

Cholecystokinin (CCK)-immunopositive interneurons in the rat perirhinal cortex. Photomicrographs showing interneurons stained with an antibody against CCK in the perirhinal cortex of 3-week-old rats (A–C). Specifically, CCK immunostaining in a control, non-epileptic rat, (A) and in pilocarpine-treated rats 3 (B) and 14 days (C) after pilocarpine treatment are respectively shown. (D) Normalized (respect to control) quantification of CCK immunostained neurons in 3 and 8-week-old rats following pilocarpine treatment. Note in the 3-week-old animals (n = 3–6 for each time interval) that CCK immunostained neurons decrease significantly 3 days after pilocarpine but recovered 7 and 14 days later. Note also that a consistent decrease in CCK-positive neurons was observed in 8-week-old rats (n = 4–5 for each time interval). **p < 0.01, analysis of variance followed by Tukey's test for multiple comparisons. Scale bar: 100 μm. Animal treatment is described in Biagini et al. (2008). Details of the immunostaining procedure and cell counts are as in Benini et al. (2011) and Gualtieri et al. (2013).
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Related In: Results  -  Collection

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Figure 7: Cholecystokinin (CCK)-immunopositive interneurons in the rat perirhinal cortex. Photomicrographs showing interneurons stained with an antibody against CCK in the perirhinal cortex of 3-week-old rats (A–C). Specifically, CCK immunostaining in a control, non-epileptic rat, (A) and in pilocarpine-treated rats 3 (B) and 14 days (C) after pilocarpine treatment are respectively shown. (D) Normalized (respect to control) quantification of CCK immunostained neurons in 3 and 8-week-old rats following pilocarpine treatment. Note in the 3-week-old animals (n = 3–6 for each time interval) that CCK immunostained neurons decrease significantly 3 days after pilocarpine but recovered 7 and 14 days later. Note also that a consistent decrease in CCK-positive neurons was observed in 8-week-old rats (n = 4–5 for each time interval). **p < 0.01, analysis of variance followed by Tukey's test for multiple comparisons. Scale bar: 100 μm. Animal treatment is described in Biagini et al. (2008). Details of the immunostaining procedure and cell counts are as in Benini et al. (2011) and Gualtieri et al. (2013).
Mentions: At variance with PV-immunopositive cells, CCK interneurons in the perirhinal cortex showed transitory changes in 3-week-old rats. This phenomenon, which may reflect functional adaptation to status epilepticus rather than cell damage, was limited to young rats whereas adult rats presented merely with loss of interneurons. As shown in Figures 7A–D, interneurons stained by an antibody against CCK (Benini et al., 2011; Gualtieri et al., 2013) were significantly (p < 0.01) reduced in 3-week-old rats at day 3 after pilocarpine treatment, but counts of these interneurons were comparable to control values at days 7 and 14 after status epilepticus. This finding could be related to a transient impairment in CCK synthesis or to an increased release. In contrast with the time course observed in the young group of animals, 8-week-old rats presented a strong reduction in CCK immunopositive cells to ~ 20% of control values, which was found at every considered time point (Figure 7D). Interestingly, these results highlight a different age-related sensitivity of CCK interneurons to pilocarpine-induced status epilepticus by confirming an enhanced resilience to damage in young animals. It remains to be established, however, whether this difference could be related to the lower propensity of young rats to develop recurrent generalized seizures when exposed to status epilepticus, in contrast to what observed in adult animals (Biagini et al., 2008).

Bottom Line: The perirhinal cortex-which is interconnected with several limbic structures and is intimately involved in learning and memory-plays major roles in pathological processes such as the kindling phenomenon of epileptogenesis and the spread of limbic seizures.However, we have recently identified in pilocarpine-treated epileptic rats the presence of selective losses of interneuron subtypes along with increased synaptic excitability.Overall, these data indicate that perirhinal cortex networks are hyperexcitable in an animal model of temporal lobe epilepsy, and that this condition is associated with a selective cellular damage that is characterized by an age-dependent sensitivity of interneurons to precipitating injuries, such as status epilepticus.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Experimental Epileptology, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia Modena, Italy.

ABSTRACT
The perirhinal cortex-which is interconnected with several limbic structures and is intimately involved in learning and memory-plays major roles in pathological processes such as the kindling phenomenon of epileptogenesis and the spread of limbic seizures. Both features may be relevant to the pathophysiology of mesial temporal lobe epilepsy that represents the most refractory adult form of epilepsy with up to 30% of patients not achieving adequate seizure control. Compared to other limbic structures such as the hippocampus or the entorhinal cortex, the perirhinal area remains understudied and, in particular, detailed information on its dysfunctional characteristics remains scarce; this lack of information may be due to the fact that the perirhinal cortex is not grossly damaged in mesial temporal lobe epilepsy and in models mimicking this epileptic disorder. However, we have recently identified in pilocarpine-treated epileptic rats the presence of selective losses of interneuron subtypes along with increased synaptic excitability. In this review we: (i) highlight the fundamental electrophysiological properties of perirhinal cortex neurons; (ii) briefly stress the mechanisms underlying epileptiform synchronization in perirhinal cortex networks following epileptogenic pharmacological manipulations; and (iii) focus on the changes in neuronal excitability and cytoarchitecture of the perirhinal cortex occurring in the pilocarpine model of mesial temporal lobe epilepsy. Overall, these data indicate that perirhinal cortex networks are hyperexcitable in an animal model of temporal lobe epilepsy, and that this condition is associated with a selective cellular damage that is characterized by an age-dependent sensitivity of interneurons to precipitating injuries, such as status epilepticus.

No MeSH data available.


Related in: MedlinePlus