Traumatic Brain Injury (TBI) remains a leading cause of morbidity and mortality in adults under 40 years old. Once primary injury occurs after TBI, neuroinflammation and oxidative stress (OS) are triggered, contributing to the development of many TBI-induced neurological deficits, and reducing the probability of critical trauma patients´ survival. Regardless the research investment on the development of anti-inflammatory and neuroprotective treatments, most pre-clinical studies have failed to report significant effects, probably because of the limited blood brain barrier permeability of no-steroidal or steroidal anti-inflammatory drugs. Lately, neurotrophic factors, such as the insulin-like growth factor 1 (IGF-1), are considered attractive therapeutic alternatives for diverse neurological pathologies, as they are neuromodulators linked to neuroprotection and anti-inflammatory effects. Considering this background, the aim of the present investigation is to test early IGF-1 gene therapy in both OS markers and cognitive deficits induced by TBI. Male Wistar rats were injected via Cisterna Magna with recombinant adenoviral vectors containing the IGF-1 gene cDNA 15 min post-TBI. Animals were sacrificed after 60 min, 24 h or 7 days to study the advanced oxidation protein products (AOPP) and malondialdehyde (MDA) levels, to recognize the protein oxidation damage and lipid peroxidation respectively, in the TBI neighboring brain areas. Cognitive deficits were assessed by evaluating working memory 7 days after TBI. The results reported significant increases of AOPP and MDA levels at 60 min, 24 h, and 7 days after TBI in the prefrontal cortex, motor cortex and hippocampus. In addition, at day 7, TBI also reduced working memory performance. Interestingly, AOPP, and MDA levels in the studied brain areas were significantly reduced after IGF-1 gene therapy that in turn prevented cognitive deficits, restoring TBI-animals working memory performance to similar values regarding control. In conclusion, early IGF-1 gene therapy could be considered a novel therapeutic approach to targeting neuroinflammation as well as to preventing some behavioral deficits related to TBI.

Background: In this paper, we report a clinical series of skull base lesions operated on trough the MiniPT, extending its application to skull base lesions, either using the classical minipterional or a variant, we call extradural minipterional approach (MiniPTEx). Methods: We describe our surgical technique of operating on complex skull base lesions using a minipterional extradural approach. Anterior clinoidectomy, middle fossa peeling, transcavernous, and Kawase approaches were performed as needed. In total, we carried out 24 surgeries: three skull base tumors, 1 Moyamoya case, and 20 giant/complex intracranial aneurysms. All the patients present good neurological result (mRs < 3). Only two patients had paralysis of any cranial nerve and only one patient had a mild hemiparesis. Results: This surgery series there are 24 cases, 10 patients were treated with exclusive MiniPT. MiniPT extradural approach was made in 14 patients. Twelve were treated using pure MiniPTEx approach, 1 patient using transcavernous approach, and in 1 patient, the anterior clinoid was resected with the combination of a MiniPT, a medium fossa peeling, and the Kawase anterior petrosectomy for skull base surgery. Conclusion: We further advance the indications of the MiniPT by extending it to operate on the cranial base tumors or complex vascular lesions without additional morbidity. MiniPT approach may be safely associated with skull base techniques, including anterior and posterior clinoidectomies, peeling of the middle fossa, transcavernous approach, and anterior petrosectomy. The versatility of the MiniPT craniotomy and the feasibility of performing skull base surgery through the MiniPT technique have been demonstrated in this paper.

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