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Perspectives for computational modeling of cell replacement for neurological disorders.

Aimone JB, Weick JP - Front Comput Neurosci (2013)

Bottom Line: The addition of nascent neurons from stem cell precursors into damaged or diseased tissue has been used as a successful therapeutic tool in recent decades.Secondly, we suggest that computational modeling of cell replacement therapies can be made feasible by implementing approaches taken by current models of adult neurogenesis.The development of these models is critical for generating hypotheses regarding transplant therapies and improving outcomes by tailoring transplants to desired effects.

View Article: PubMed Central - PubMed

Affiliation: 1Cognitive Modeling Group, Sandia National Laboratories Albuquerque, NM, USA.

ABSTRACT
Mathematical modeling of anatomically-constrained neural networks has provided significant insights regarding the response of networks to neurological disorders or injury. A logical extension of these models is to incorporate treatment regimens to investigate network responses to intervention. The addition of nascent neurons from stem cell precursors into damaged or diseased tissue has been used as a successful therapeutic tool in recent decades. Interestingly, models have been developed to examine the incorporation of new neurons into intact adult structures, particularly the dentate granule neurons of the hippocampus. These studies suggest that the unique properties of maturing neurons, can impact circuit behavior in unanticipated ways. In this perspective, we review the current status of models used to examine damaged CNS structures with particular focus on cortical damage due to stroke. Secondly, we suggest that computational modeling of cell replacement therapies can be made feasible by implementing approaches taken by current models of adult neurogenesis. The development of these models is critical for generating hypotheses regarding transplant therapies and improving outcomes by tailoring transplants to desired effects.

No MeSH data available.


Related in: MedlinePlus

Spiking properties of hPSNs.(A–C) Voltage clamp traces of three different hPSNs during current injection illustrating various spiking capabilities including RS (A), IS (B), and delayed spiking (C).
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Figure 1: Spiking properties of hPSNs.(A–C) Voltage clamp traces of three different hPSNs during current injection illustrating various spiking capabilities including RS (A), IS (B), and delayed spiking (C).

Mentions: Unfortunately, most publications measuring functional properties of hPSNs demonstrate report only RS phenotypes (Wernig et al., 2004; Johnson et al., 2007; Wu et al., 2007). In our hands, hPSNs derived from the WA09 (H9) cell line display primarily RS neurons with a frequency range of 10 to 36 Hz (Figure 1A). In approximately 10% of cells however, we observed delayed spiking phenotype (Figure 1B), while an even smaller minority displayed IS behavior (Figure 1C), with no evidence of IB neurons. However, it is likely that that the dearth of variation is partially due to the immature nature of most hPSNs reported, as many display relatively depolarized resting membrane potentials (RMP) and diminishing action potential (AP) amplitude during current pulses (Johnson et al., 2007).


Perspectives for computational modeling of cell replacement for neurological disorders.

Aimone JB, Weick JP - Front Comput Neurosci (2013)

Spiking properties of hPSNs.(A–C) Voltage clamp traces of three different hPSNs during current injection illustrating various spiking capabilities including RS (A), IS (B), and delayed spiking (C).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3818471&req=5

Figure 1: Spiking properties of hPSNs.(A–C) Voltage clamp traces of three different hPSNs during current injection illustrating various spiking capabilities including RS (A), IS (B), and delayed spiking (C).
Mentions: Unfortunately, most publications measuring functional properties of hPSNs demonstrate report only RS phenotypes (Wernig et al., 2004; Johnson et al., 2007; Wu et al., 2007). In our hands, hPSNs derived from the WA09 (H9) cell line display primarily RS neurons with a frequency range of 10 to 36 Hz (Figure 1A). In approximately 10% of cells however, we observed delayed spiking phenotype (Figure 1B), while an even smaller minority displayed IS behavior (Figure 1C), with no evidence of IB neurons. However, it is likely that that the dearth of variation is partially due to the immature nature of most hPSNs reported, as many display relatively depolarized resting membrane potentials (RMP) and diminishing action potential (AP) amplitude during current pulses (Johnson et al., 2007).

Bottom Line: The addition of nascent neurons from stem cell precursors into damaged or diseased tissue has been used as a successful therapeutic tool in recent decades.Secondly, we suggest that computational modeling of cell replacement therapies can be made feasible by implementing approaches taken by current models of adult neurogenesis.The development of these models is critical for generating hypotheses regarding transplant therapies and improving outcomes by tailoring transplants to desired effects.

View Article: PubMed Central - PubMed

Affiliation: 1Cognitive Modeling Group, Sandia National Laboratories Albuquerque, NM, USA.

ABSTRACT
Mathematical modeling of anatomically-constrained neural networks has provided significant insights regarding the response of networks to neurological disorders or injury. A logical extension of these models is to incorporate treatment regimens to investigate network responses to intervention. The addition of nascent neurons from stem cell precursors into damaged or diseased tissue has been used as a successful therapeutic tool in recent decades. Interestingly, models have been developed to examine the incorporation of new neurons into intact adult structures, particularly the dentate granule neurons of the hippocampus. These studies suggest that the unique properties of maturing neurons, can impact circuit behavior in unanticipated ways. In this perspective, we review the current status of models used to examine damaged CNS structures with particular focus on cortical damage due to stroke. Secondly, we suggest that computational modeling of cell replacement therapies can be made feasible by implementing approaches taken by current models of adult neurogenesis. The development of these models is critical for generating hypotheses regarding transplant therapies and improving outcomes by tailoring transplants to desired effects.

No MeSH data available.


Related in: MedlinePlus