Using templated agarose scaffolds to promote axon regeneration through sites of spinal cord injury.

The past 30 years of research in spinal cord injury (SCI) have revealed that, under certain conditions, some types of axons are able to regenerate. To aid these axons in bridging the lesion site, many experimenters place cellular grafts at the lesion. However, to increase the potential for functional recovery, it is likely advantageous to maximize the number of axons that reach the intact spinal cord on the other side of the lesion.

Motor axonal regeneration after partial and complete spinal cord transection.

We subjected rats to either partial midcervical or complete upper thoracic spinal cord transections and examined whether combinatorial treatments support motor axonal regeneration into and beyond the lesion. Subjects received cAMP injections into brainstem reticular motor neurons to stimulate their endogenous growth state, bone marrow stromal cell grafts in lesion sites to provide permissive matrices for axonal growth, and brain-derived neurotrophic factor gradients beyond the lesion to stimulate distal growth of motor axons. Findings were compared with several control groups.

PTEN deletion enhances the regenerative ability of adult corticospinal neurons.

Despite the essential role of the corticospinal tract (CST) in controlling voluntary movements, successful regeneration of large numbers of injured CST axons beyond a spinal cord lesion has never been achieved. We found that PTEN/mTOR are critical for controlling the regenerative capacity of mouse corticospinal neurons. After development, the regrowth potential of CST axons was lost and this was accompanied by a downregulation of mTOR activity in corticospinal neurons.

Matrix metalloproteinase-7 facilitates immune access to the CNS in experimental autoimmune encephalomyelitis.

Background: Metalloproteinase inhibitors can protect mice against experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS). Matrix metalloproteinase-9 (MMP-9) has been implicated, but it is not clear if other MMPs are also involved, including matrilysin/MMP-7 - an enzyme capable of cleaving proteins that are essential for blood brain barrier integrity and immune suppression.

Results: Here we report that MMP-7-deficient (mmp7-/-) mice on the C57Bl/6 background are resistant to EAE induced by myelin oligodendrocyte glycoprotein (MOG).

Electrically evoked locomotor activity in the turtle spinal cord hemi-enlargement preparation.

We assessed the locomotor capacity of the left half of the spinal cord hindlimb enlargement in low-spinal turtles. Forward swimming was evoked in the left hindlimb by electrical stimulation of the right dorsolateral funiculus (DLF) at the anterior end of the third postcervical spinal segment (D3). Animals were held by a band-clamp in a water-filled tank so that hindlimb movements could be recorded from below with a digital video camera.

Location of spinal cord pathways that control hindlimb movement amplitude and interlimb coordination during voluntary swimming in turtles.

We performed mechanical lesions of the midbody (D2-D3; second to third postcervical spinal segments) spinal cord in otherwise intact turtles to locate spinal cord pathways that 1) activate and control the amplitude of voluntary hindlimb swimming movements and 2) coordinate hindlimb swimming with the movement of other limbs. Pre- and postlesion turtles were held by a band clamp around the carapace just beneath the water surface in a clear Plexiglas tank and videotaped from below so that kinematic measurements could be made of voluntary forward swimming with motion analysis software. Movements of the forelimbs (wrists) and hindlimbs (knees and ankles) were tracked relative to stationary reference points on the plastron to obtain bilateral measurements of hip and forelimb angles as functions of time along with foot trajectories.

Crossed commissural pathways in the spinal hindlimb enlargement are not necessary for right left hindlimb alternation during turtle swimming.

We examined the coordination between right and left hindlimbs during voluntary forward swimming in adult red-eared turtles, before and after midsagittal section of the spinal cord hindlimb enlargement (segments D8-S2) or the enlargement plus the first preenlargement segment (D7-S2). Our purpose was to assess the role of crossed commissural axons in these segments for right-left hindlimb alternation during voluntary locomotion. Midsagittal splitting severed commissural fibers and separated the right and left halves of the posterior spinal cord.