Molecular and Cellular Biochemistry

, Volume 369, Issue 1–2, pp 267–286 | Cite as

Gene expression changes of interconnected spared cortical neurons 7 days after ischemic infarct of the primary motor cortex in the rat

  • Edward T. R. UrbanIII
  • Scott D. Bury
  • H. Scott Barbay
  • David J. Guggenmos
  • Yafeng Dong
  • Randolph J. Nudo
Article

Abstract

After cortical injury resulting from stroke, some recovery can occur and may involve spared areas of the cerebral cortex reorganizing to assume functions previously controlled by the damaged cortical areas. No studies have specifically assessed gene expression changes in remote neurons with axonal processes that terminate in the infarcted tissue, i.e., the subset of neurons most likely to be involved in regenerative processes. By physiologically identifying the primary motor area controlling forelimb function in adult rats (caudal forelimb area = CFA), and injecting a retrograde tract-tracer, we labeled neurons within the non-primary motor cortex (rostral forelimb area = RFA) that project to CFA. Then, 7 days after a CFA infarct (n = 6), we used laser capture microdissection techniques to harvest labeled neurons in RFA. Healthy, uninjured rats served as controls (n = 6). Biological interactions and functions of gene profiling were investigated by Affymetrix Microarray, and Ingenuity Pathway Analysis. A total of 143 up- and 128 down-regulated genes showed significant changes (fold change ≥1.3 and p < 0.05). The canonical pathway, “Axonal Guidance Signaling,” was overrepresented (p value = 0.002). Significantly overrepresented functions included: branching of neurites, organization of cytoskeleton, dendritic growth and branching, organization of cytoplasm, guidance of neurites, development of cellular protrusions, density of dendritic spines, and shape change (p = 0.000151–0.0487). As previous studies have shown that spared motor areas are important in recovery following injury to the primary motor area, the results suggest that these gene expression changes in remote, interconnected neurons may underlie reorganization and recovery mechanisms.

Keywords

Stroke Ischemic infarct Motor cortex Plasticity Gene expression 

Abbreviations

CFA

Caudal forelimb area

RFA

Rostral forelimb area

PMv

Ventral premotor area

S1

Primary sensory area

M1

Primary motor area

ICMS

Intracortical microstimulation

CTB647

Cholera toxin beta subunit conjugated to AlexaFluor 647

LCM

Laser capture microdissection

IPA

Ingenuity pathway analysis

IM

Intermuscular

IP

Interperitoneal

IVT

In vitro transcription

RIN

RNA integrity number

RMA

Robust multi-array averaging

NeuN

Neuronal nuclei antigen

RNA

Ribonucleic acid

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Copyright information

© Springer Science+Business Media, LLC. 2012

Authors and Affiliations

  • Edward T. R. UrbanIII
    • 1
    • 2
  • Scott D. Bury
    • 2
  • H. Scott Barbay
    • 2
  • David J. Guggenmos
    • 1
    • 2
  • Yafeng Dong
    • 3
  • Randolph J. Nudo
    • 1
    • 2
    • 4
  1. 1.Department of Molecular & Integrative PhysiologyKansas University Medical CenterKansas CityUSA
  2. 2.Landon Center on AgingKansas University Medical CenterKansas CityUSA
  3. 3.Department of Obstetrics and GynecologyKansas University Medical CenterKansas CityUSA
  4. 4.Intellectual & Developmental Disabilities Research CenterKansas University Medical CenterKansas CityUSA

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