Prevention of epidural fibrosis with ADCON-L in presence of a durotomy during lumbar disc surgery: experiences with a pre-clinical model.

A potential complication of lumbo-sacral surgery is the inadvertent tear of the dura mater, which sometimes eludes intra-operative detection. ADCON-L, a bioabsorbable gel used in lumbosacral laminectomies or laminotomies, is a physical barrier to post-operative epidural fibrosis. Three experimental lumbar laminectomy studies were designed to assess in vivo the effects of ADCON-L when applied in presence of dural punctures in a rat model. In the first study, the durotomy was repaired with fibrin sealant, in the second experiment the dural defect was microsurgically sutured, while in a third protocol the durotomy was left unrepaired. In each study, dural healing was assessed respectively at 4, 8, or 12 weeks post-operatively. Blinded anatomical dissection and histopathology were used to compare results between treatments (sham operated control vs. ADCON-L). In the fibrin sealant experiment, an additional treatment group (fibrin sealant used together with ADCON-L) was included. The results of these studies consistently demonstrate that ADCON-L is an effective anti-fibrotic agent, and does not interfere with the normal dural healing processes following a meningeal puncture. The application of the gel may therefore be safe in presence of dural incisions, even when they are not identified during surgery, as demonstrated in these in vivo studies.

ADCON-T/N reduces in vivo perineural adhesions in a rat sciatic nerve reoperation model.

Excessive perineural scarring may affect the result of peripheral nerve surgery. The ability of a novel implant material (ADCON-T/N) to prevent this complication was tested in 38 rats. Four weeks after a bilateral sciatic nerve external neurolysis, a secondary bilateral lysis of the adhesions was performed; ADCON-T/N was locally implanted at one side, while the contralateral side was left untreated. Four or 8 weeks later, perineural adhesions were dissected in 24 animals and graded blindly. Significantly fewer perineural adhesions were found in ADCON-T/N treated nerves compared with controls at both 4 and 8 weeks. Residual implant material or adverse effects were not observed at either time. Histological examination of the neurolysis sites in another 14 animals confirmed these findings at both time intervals. This study shows that ADCON-T/N is effective in inhibiting perineural adhesions, is resorbed within 4 weeks and is well tolerated.

Accumulation of the beta amyloid precursor protein at sites of ischemic injury in rat brain.

We used various antibodies to the beta amyloid precursor protein (APP) of Alzheimer's disease to study changes in the cellular distribution of APP in experimental ischemic brain injury. In contrast to sham operated controls, rats with repeated reversible occlusions of one middle cerebral artery showed striking APP reactivity in astrocytic processes in perifocal regions and white matter tracts. Dystrophic axons and neurons with accumulated APP were also evident in the ipsilateral neocortex and hippocampus. Such changes were also apparent in rats subjected to partial forebrain ischemia by bilateral occlusion of the carotid arteries. Our studies suggest that focal ischemic insults or chronic hypoperfusion leads to increased accumulation of APP in surviving brain cells that may pertain to enhanced beta amyloid deposition in Alzheimer's disease.