NNS 2015 Abstract Book

Ohio State University, School of Health and Rehabilitation Sciences,

Columbus, USA

Ohio State University, Neuroscience, Columbus, USA

Ohio State University, Neuroscience Graduate Studies Program,

Columbus, USA

Mallinckrodt Pharmaceuticals, Medical Science Liaison, St. Louis, USA

Ohio State University, College of Dentistry, Columbus, USA

Spinal cord injury results in a series of cellular cascades at the injury

site which are largely comprised of inflammatory processes. Con-

siderable research has been dedicated to cellular events at the epi-

center but little is known about changes in the blood brain barrier

remote to the primary injury site. This presentation will discuss the

latest evidence showing: 1) the physiological response of the blood

brain barrier to exercise; 2) active trafficking of peripheral monocytes

into the lumbar spinal cord after mid-thoracic contusion; and 3)

passive permeability of the barrier after spinal cord contusion. The

role of these changes in promoting an inflammatory microenviron-

ment and the implications for functional recovery will be discussed.

Keywords: Lumbar cord, remote effects, activity-dependent, Lamina 10

S09-02

MICROGLIAL ACTIVATION AND THE RECRUITMENT OF

MONOCYTES TO THE CNS: LESSONS LEARNED FROM

MODELS OF PSYCHOLOGICAL STRESS AND SCI

Jonathan Godbout

The Ohio State University, Neuroscience, Columbus, USA

Recruitment of immune cells may be beneficial or detrimental to in-

trinsic repair processes after CNS injury. Mounting evidence indicates

that the activation profile of the resident microglia (M1 or M2) influ-

ences the recruitment of immune cells to the CNS. From our work in

other models we have gained insight into the dynamics of microglia

activation and monocyte recruitment. For instance, repeated social de-

feat (RSD), a psychological stressor, activates microglia and promotes

the recruitment of monocytes to the brain. Following RSD, microglia

preferentially secrete chemokines and monocyte recruitment is depen-

dent on chemokine receptor interactions including chemokine receptor-

2 and fractalkine receptor. Moreover, monocytes are recruited to spe-

cific areas of the brain where microglial activation is robust. The

monocytes that are recruited to the brain are inflammatory (CCR2

CD45

/Ly6C

) and produce high levels of interleukin-1b. Importantly

the consequence of this increased recruitment of ‘‘inflammatory’’

monocytes to the brain is the development of anxiety-like behavior.

Furthermore, the disruption of microglial activation, prevention of

monocyte recruitment, or blockade of IL-1b signaling, all ameliorate the

stress-induced anxiety. Building on this work, we have also detected

selective recruitment of monocytes after SCI. This is associated with an

M2a profile of microglia. This active recruitment of monocytes that

become ‘‘repair’’ macrophages (IL-4Ra

/Arg

), however, is impaired in

older mice and is associated with reduced functional recovery after SCI.

Overall, data are highlighted from models of stress and SCI that may

provide insight into the mechanisms by which microglia help to se-

lectively recruit monocytes to the CNS.

Keywords: Neuroimmunology, Stress, Monocytes, microglia, SCI

S09-03

EXERCISE AFTER TRAUMATIC BRAIN INJURY: IS IT A

DOUBLE-EDGED SWORD?

Grace Griesbach

Centre for NeuroSkills, Research, Encino, USA

This talk will focus on challenges implementing exercise after trau-

matic brain injury. (TBI). Exercise has been proven valuable because

it increases proteins that are important in neuronal plasticity and re-

pair. Although exercise helps the brain recover from injury it may

impair recovery if it takes place during the early post injury period and

is associated with stress. The critical nature of the timing of experi-

ence-dependent rehabilitative interventions during different post-

traumatic injury periods will be discussed. Stress influences the neu-

roplasticity and response to rehabilitative interventions. Thus, neu-

roendoctine responses to brain injury and exercise will also be

addressed. The implications of neuroendocrine dysregulation will

have an influence on the timing of rehabilitation as well as the return

to athletic activities following a concussion. Finally some of the

challenges of translating the basic science of concussion and exercise

will be discussed.

Keywords: exercise, neuroendocrine, mild TBI, stress

S10 Open Communication: TBI

S10-01

PREVENTING POSTTRAUMATIC EPILEPTOGENESIS BY

STIMULATING CORTICAL EXCITATORY ACTIVITY

AFTER TRAUMATIC BRAIN INJURY

Xiaoming Jin

1,2

, Xingjie Ping

1,2

, Wenhui Xiong

1,2

, Grace Chavez

1,2

Jianhua Gao

1,2

Indiana University School of Medicine, Anatomy and Cell Biology,

Indianapolis, USA

Indiana University School of Medicine, Spinal Cord and Brain Injury

Research Group, Indianapolis, USA

Homeostatic synaptic plasticity has been proposed to underlie ac-

quired epileptogenesis. This hypothesis suggests that loss of neuro-

nal activity following brain injury will initiate epileptogenesis while

stimulating neuronal activity may prevent it. However, whether

stimulating neuronal activity can prevent posttraumatic epilepto-

genesis has not been directly tested. In the partially isolated neo-

cortex model of posttraumatic epileptogenesis (undercut) in mice,

we made patch clamp recording from cortical layer V pyramidal

neurons and found that spontaneous action potential firings in these

neurons were significantly reduced at both 1 and 7 days after injury.

The frequencies of both spontaneous excitatory and inhibitory syn-

aptic currents (sEPSCs and sIPSCs) were also significantly de-

pressed but without significant changes in the amplitudes of these

events. In Thy1-channelrhodopsin-2 (ChR2) transgenic mice that

express ChR2 in cortical layer V pyramidal neurons, we made un-

dercut injury and applied optogenetic stimulation of the injured

cortex using LED light for 7 days

in vivo

. Chronic optogenetic

stimulation resulted in increased seizure threshold as indicated by a

higher drug dosage required for inducing seizure and a longer la-

tency period in pentylenetetrazol (PTZ) test, and reduced cortical

hyperexcitability as indicated by decreases in the percentages of

slices and mice in which epileptiform activity could be evoked in

field potential recording. The frequencies of both sEPSCs and

sIPSCs in neurons after optogenetic stimulation were significantly

lower that the control undercut mice. The results support that ho-

meostatic plasticity plays a role in the posttraumatic epileptogenesis

and that stimulating activity of cortical excitatory neurons has pro-

phylactic effect on posttraumatic epileptogenesis.

Keywords: Homeostatic plasticity, Optogenetic, Posttraumatic

epileptogenesis, Cerebral cortex

A-143