Neuroprotection against surgically induced brain injury

Abstract

Background: Neurosurgical procedures are carried out routinely in health institutions across the world. A key issue to be considered during neurosurgical interventions is that there is always an element of inevitable brain injury that results from the procedure itself because of the unique nature of the nervous system. Brain tissue at the periphery of the operative site is at risk of injury by various means, including incisions and direct trauma, electrocautery, hemorrhage, and retractor stretch.

Methods/results: In the present review, we will elaborate upon this surgically induced brain injury and also present a novel animal model to study it. In addition, we will summarize preliminary results obtained by pretreatment with PP1, an Src tyrosine kinase inhibitor reported to have neuroprotective properties in in vivo experimental studies. Any form of pretreatment to limit the damage to the susceptible functional brain tissue during neurosurgical procedures may have a significant impact on patient recovery.

Conclusion: This brief review is intended to raise the question of 'neuroprotection against surgically induced brain injury' in the neurosurgical scientific community and stimulate discussions.

Figure 1

Left panel depicts a rat brain cut along horizontal plane and shows the frontal lobe surgical injury in relation to the bregma (marked by X). The two incisions are made leading away from the bregma along the sagittal and coronal planes 2 mm lateral and 1 mm proximal to the sagittal and coronal sutures respectively. The right panel is a 3D image of the proposed model showing the frontal lobe surgical injury (in red) from different angles and planes.

Figure 2

The figure shows marked edema in the frontal ipsilateral (bordering the surgical-injury) brain in untreated and PP1-treated groups as compared to the control group 24 hrs after the surgical-injury. The brain edema, however, is significantly lowered in the group that is pretreated (45 mins before surgery) with src tyrosine kinase inhibitor, PP1 (1.5mg/kg, i.p.) as compared to untreated group. The other brain regions did not differ statistically from each other after the injury. p< 0.05 for both * and # which represent vs control and vs untreated respectively. Data are expressed as mean ± S.E.M. Statistical significance was verified by one-way analysis of variance (ANOVA) for multiple comparisons.

Figure 3

The representative figure (n=4) in the upper panel shows IgG staining in a horizontal section of the brain 24 hours after the frontal lobe surgical injury. There is increased IgG staining surrounding the surgically-induced brain injury (marked by arrows) on the ipsilateral side as compared to the unaffected contralateral side indicated by the asterisk (*). The lower panel shows an individual affected blood vessel at high magnification depicting disruption of blood brain barrier as indicated by IgG staining. Scale represents 4 mm and 100 μm in upper and lower panels respectively.

Figure 4

The representative figures (n=4) show Nissl’s staining in a horizontal section of the brain 24 hours after the frontal lobe surgical injury. There is a marked area comprising of dead cells adjoining the surgically-induced brain injury (marked by arrows at low magnification) on the ipsilateral side. A transition zone marks the merging of this affected area with the unaffected viable cells as marked by the yellow broken line. Scale represents 200 μm.