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What Elements of the Inflammatory System Are Necessary for Epileptogenesis In Vitro?(1,2).

Park KI, Dzhala V, Saponjian Y, Staley KJ - eNeuro (2015)

Bottom Line: Organotypic hippocampal brain slices can be maintained in culture independently of the systemic inflammatory system, and the rapid course of epileptogenesis in these cultures supports the idea that inflammation is not necessary for epilepsy.However, this preparation still retains key cellular inflammatory mediators.These data support the idea that although the inflammatory system, neurons, and glia share key intercellular signaling molecules, neither systemic nor CNS-specific cellular elements of the immune and inflammatory systems are necessary components of epileptogenesis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurology, Massachusetts General Hospital , Boston, Massachusetts 02129 ; Seoul Paik Hospital, Inje University , Seoul 100-032, South Korea.

ABSTRACT
Epileptogenesis in vivo can be altered by manipulation of molecules such as cytokines and complement that subserve intercellular signaling in both the inflammatory and central nervous systems. Because of the dual roles of these signaling molecules, it has been difficult to precisely define the role of systemic inflammation in epileptogenesis. Organotypic hippocampal brain slices can be maintained in culture independently of the systemic inflammatory system, and the rapid course of epileptogenesis in these cultures supports the idea that inflammation is not necessary for epilepsy. However, this preparation still retains key cellular inflammatory mediators. Here, we found that rodent hippocampal organotypic slice cultures depleted of T lymphocytes and microglia developed epileptic activity at essentially the same rate and to similar degrees of severity as matched control slice cultures. These data support the idea that although the inflammatory system, neurons, and glia share key intercellular signaling molecules, neither systemic nor CNS-specific cellular elements of the immune and inflammatory systems are necessary components of epileptogenesis.

No MeSH data available.


Related in: MedlinePlus

Effect of microglial depletion on epileptogenesis and ictogenesis in wild-type mice slices. A, Data was recorded at DIV6 after exposure of liposome clodronate from DIV0 to 6. B, Data was recorded at DIV12 after exposure of liposomal clodronate from DIV6 to 12. Microglial depletion did not alter the frequency, total duration, or mean duration of seizure-like activities (n = 4-5 per group). C, Representative traces recorded at DIV6 from microglia-depleted and control group, shows similar patterns of spontaneous seizure-like activities. All values are expressed as mean ± SEM. N.S, Not significant.
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Figure 4: Effect of microglial depletion on epileptogenesis and ictogenesis in wild-type mice slices. A, Data was recorded at DIV6 after exposure of liposome clodronate from DIV0 to 6. B, Data was recorded at DIV12 after exposure of liposomal clodronate from DIV6 to 12. Microglial depletion did not alter the frequency, total duration, or mean duration of seizure-like activities (n = 4-5 per group). C, Representative traces recorded at DIV6 from microglia-depleted and control group, shows similar patterns of spontaneous seizure-like activities. All values are expressed as mean ± SEM. N.S, Not significant.

Mentions: Clodronate is a selective macrophagic and microglial toxin without evidence of injury to other cellular components (Kohl et al. 2003; Kumamaru et al., 2012). Perivascular macrophages could be retained in slice cultures, but these cells are also depleted by clodromate at concentrations below those needed to deplete microglia (Polfliet et al., 2001). To assess whether microglia alter the course of epileptogenesis or ictogenesis, we incubated slice cultures in clodronate-encapsulated liposomes (Clodrosome, purchased at www.clodrosome.com, containing 17 mM of clodronate disodium salt, 24 mM of phosphatidylcholine, and 11 mM of cholesterol suspended in PBS) for 3-6 d, as specified in the Results (Fig. 4A). During these incubations, Clodrosome was replenished with each media change.


What Elements of the Inflammatory System Are Necessary for Epileptogenesis In Vitro?(1,2).

Park KI, Dzhala V, Saponjian Y, Staley KJ - eNeuro (2015)

Effect of microglial depletion on epileptogenesis and ictogenesis in wild-type mice slices. A, Data was recorded at DIV6 after exposure of liposome clodronate from DIV0 to 6. B, Data was recorded at DIV12 after exposure of liposomal clodronate from DIV6 to 12. Microglial depletion did not alter the frequency, total duration, or mean duration of seizure-like activities (n = 4-5 per group). C, Representative traces recorded at DIV6 from microglia-depleted and control group, shows similar patterns of spontaneous seizure-like activities. All values are expressed as mean ± SEM. N.S, Not significant.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4596089&req=5

Figure 4: Effect of microglial depletion on epileptogenesis and ictogenesis in wild-type mice slices. A, Data was recorded at DIV6 after exposure of liposome clodronate from DIV0 to 6. B, Data was recorded at DIV12 after exposure of liposomal clodronate from DIV6 to 12. Microglial depletion did not alter the frequency, total duration, or mean duration of seizure-like activities (n = 4-5 per group). C, Representative traces recorded at DIV6 from microglia-depleted and control group, shows similar patterns of spontaneous seizure-like activities. All values are expressed as mean ± SEM. N.S, Not significant.
Mentions: Clodronate is a selective macrophagic and microglial toxin without evidence of injury to other cellular components (Kohl et al. 2003; Kumamaru et al., 2012). Perivascular macrophages could be retained in slice cultures, but these cells are also depleted by clodromate at concentrations below those needed to deplete microglia (Polfliet et al., 2001). To assess whether microglia alter the course of epileptogenesis or ictogenesis, we incubated slice cultures in clodronate-encapsulated liposomes (Clodrosome, purchased at www.clodrosome.com, containing 17 mM of clodronate disodium salt, 24 mM of phosphatidylcholine, and 11 mM of cholesterol suspended in PBS) for 3-6 d, as specified in the Results (Fig. 4A). During these incubations, Clodrosome was replenished with each media change.

Bottom Line: Organotypic hippocampal brain slices can be maintained in culture independently of the systemic inflammatory system, and the rapid course of epileptogenesis in these cultures supports the idea that inflammation is not necessary for epilepsy.However, this preparation still retains key cellular inflammatory mediators.These data support the idea that although the inflammatory system, neurons, and glia share key intercellular signaling molecules, neither systemic nor CNS-specific cellular elements of the immune and inflammatory systems are necessary components of epileptogenesis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Neurology, Massachusetts General Hospital , Boston, Massachusetts 02129 ; Seoul Paik Hospital, Inje University , Seoul 100-032, South Korea.

ABSTRACT
Epileptogenesis in vivo can be altered by manipulation of molecules such as cytokines and complement that subserve intercellular signaling in both the inflammatory and central nervous systems. Because of the dual roles of these signaling molecules, it has been difficult to precisely define the role of systemic inflammation in epileptogenesis. Organotypic hippocampal brain slices can be maintained in culture independently of the systemic inflammatory system, and the rapid course of epileptogenesis in these cultures supports the idea that inflammation is not necessary for epilepsy. However, this preparation still retains key cellular inflammatory mediators. Here, we found that rodent hippocampal organotypic slice cultures depleted of T lymphocytes and microglia developed epileptic activity at essentially the same rate and to similar degrees of severity as matched control slice cultures. These data support the idea that although the inflammatory system, neurons, and glia share key intercellular signaling molecules, neither systemic nor CNS-specific cellular elements of the immune and inflammatory systems are necessary components of epileptogenesis.

No MeSH data available.


Related in: MedlinePlus