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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 ictogenesis in cultured rat slices. A, Schematic drawing of experiment protocol. B, Representative traces of field potentials recorded at DIV22 show that the microglia-depleted slice had more frequent and longer seizure-like activities compared to the control slice. C, Bar graphs indicate the percentage of slices with more than one seizure-like activity during observation period in each group. D−F, The frequency of seizure-like activities was significantly greater in the microglia-depleted group (13.3 ± 3.1 vs 3.9 ± 2.1/h, n = 11 per group, p = 0.02). All values are expressed as mean ± SEM, *p < 0.05.
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Figure 2: Effect of microglial depletion on ictogenesis in cultured rat slices. A, Schematic drawing of experiment protocol. B, Representative traces of field potentials recorded at DIV22 show that the microglia-depleted slice had more frequent and longer seizure-like activities compared to the control slice. C, Bar graphs indicate the percentage of slices with more than one seizure-like activity during observation period in each group. D−F, The frequency of seizure-like activities was significantly greater in the microglia-depleted group (13.3 ± 3.1 vs 3.9 ± 2.1/h, n = 11 per group, p = 0.02). All values are expressed as mean ± SEM, *p < 0.05.

Mentions: We compared spontaneous SLAs at DIV22 according to the presence or absence of microglia (n = 11 each group). Equal numbers of slices from each animal were allocated to clodronate or control groups. Extracellular field potentials were recorded for 1 h in each slice. All slices showed at least one SLA in the microglia-depleted group and only 72.7% showed SLA in the control group (p = 0.07d; Fig. 2C). The frequency of SLA in microglia-depleted slices was significantly higher than control (13.3 ± 3.1 vs 3.9 ± 2.1 SLA/h; p = 0.02e; Fig. 2D). Total duration (13.4 ± 4.1 vs 4.3 ± 3.5 min; p = 0.11f; Fig. 2E) and mean duration of each SLA (2.1 ± 0.9 vs 0.5 ± 0.2 min; p = 0.14g; Fig. 2F) were longer in microglia-depleted slices than control, but the differences did not reach statistical significance.


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 ictogenesis in cultured rat slices. A, Schematic drawing of experiment protocol. B, Representative traces of field potentials recorded at DIV22 show that the microglia-depleted slice had more frequent and longer seizure-like activities compared to the control slice. C, Bar graphs indicate the percentage of slices with more than one seizure-like activity during observation period in each group. D−F, The frequency of seizure-like activities was significantly greater in the microglia-depleted group (13.3 ± 3.1 vs 3.9 ± 2.1/h, n = 11 per group, p = 0.02). All values are expressed as mean ± SEM, *p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Effect of microglial depletion on ictogenesis in cultured rat slices. A, Schematic drawing of experiment protocol. B, Representative traces of field potentials recorded at DIV22 show that the microglia-depleted slice had more frequent and longer seizure-like activities compared to the control slice. C, Bar graphs indicate the percentage of slices with more than one seizure-like activity during observation period in each group. D−F, The frequency of seizure-like activities was significantly greater in the microglia-depleted group (13.3 ± 3.1 vs 3.9 ± 2.1/h, n = 11 per group, p = 0.02). All values are expressed as mean ± SEM, *p < 0.05.
Mentions: We compared spontaneous SLAs at DIV22 according to the presence or absence of microglia (n = 11 each group). Equal numbers of slices from each animal were allocated to clodronate or control groups. Extracellular field potentials were recorded for 1 h in each slice. All slices showed at least one SLA in the microglia-depleted group and only 72.7% showed SLA in the control group (p = 0.07d; Fig. 2C). The frequency of SLA in microglia-depleted slices was significantly higher than control (13.3 ± 3.1 vs 3.9 ± 2.1 SLA/h; p = 0.02e; Fig. 2D). Total duration (13.4 ± 4.1 vs 4.3 ± 3.5 min; p = 0.11f; Fig. 2E) and mean duration of each SLA (2.1 ± 0.9 vs 0.5 ± 0.2 min; p = 0.14g; Fig. 2F) were longer in microglia-depleted slices than control, but the differences did not reach statistical significance.

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