Models of movement disorders and neurodegeneration

Option A – Surgical ablation of a defined cortical territory. The dura is opened and a precisely delimited piece of the primary motor cortex, bounded by identified sulcal landmarks and of predetermined surface area and depth, is removed under the operating microscope. This produces a lesion whose volume, borders and laminar extent are defined by the surgeon rather than by the tissue’s response to a mechanical insult, which gives the lowest inter-animal variability and leaves a clean-walled cavity — the configuration best suited to intracortical cell grafting and to hydrogel or scaffold delivery.

Option B – Controlled cortical impact. A controlled cortical impact (CCI) device is positioned over the exposed dura mater and the impact is delivered to the motor cortex at a depth, velocity and dwell time set from pilot studies to induce a consistent injury. This reproduces the biomechanics of a closed mechanical insult and the secondary injury cascade that follows it – contusion, oedema, haemorrhage, blood–brain barrier disruption and perilesional neuroinflammation – and is therefore the option of choice when the therapeutic hypothesis concerns the acute and subacute injury response rather than the replacement of lost tissue.

In both options, haemostasis is achieved with sterile saline irrigation and haemostatic agents, the bone flap is replaced and secured, and the incision is closed; animals recover under close monitoring with postoperative analgesia. Test items may be administered intracortically into or around the lesion, intracerebrally, orally, by gavage, or by subcutaneous, intramuscular or intraperitoneal routes, acutely or chronically. If the test item is a cell therapy, initiate a tri-therapy immunosuppressive regimen one month before grafting and maintain it throughout the in-life phase, with weekly haematology, renal, and hepatic monitoring and therapeutic drug monitoring to adjust dosing.