Modulation of the immune response by focused ultrasound suppressed brain abscess formation.

Abstract

Brain abscess is a serious, life-threatening intracranial infection caused by inflammation and collection of infected material. Given the rise of multi-drug resistant strains and the widespread presence of bacteria, it is probable that the incidence of brain abscesses is expected to endure. The sequela of brain abscess constitutes a major source of morbidity and mortality. Brain abscess may cause permanent neurological damage, such as paresis, hydrocephalus, spasticity, mental deterioration and epileptic seizure. Current therapeutic approaches include surgical excision or drainage combined with prolonged antimicrobial treatment usually lasting 6-8 weeks. However, extended antimicrobial treatment may cause adverse side effects, such as nephrotoxicity, ototoxicity, and bone marrow suppression. As a result, it is essential to develop a novel approach to facilitate antibiotics delivery and shorten the therapeutic course clinically. Recently, focused ultrasound (FUS) has been demonstrated to have an ability to temporally open the brain blood barrier (BBB) and modulate the immune response in the brain tumor animal model or in naïve animals. In our study, we demonstrated the focused ultrasound treatment (3W acoustic power, 0.6 MPa peak negative pressure) to treat brain abscess by boosting immune response in CNS infection in the brain abscess animal model. The size of the brain abscess is reduced by 50 percent when the MRI scan is taken at 3 weeks post-treatment. The animals get better recovery after treatment. The use of low intensity FUS with systemic microbubble infusion to open the BBB by mechanical acoustic cavitation elicited an immediate immune response including elevations in proinflmmatory cytokine (IL-1, TNFα and IL-6) in the brain parenchyma surround the brain abscess. Furthermore, FUS exposure treatment also activated glial cells, potentially enhancing the encapsulation of brain abscesses and reducing the spread of bacteria to the adjacent brain parenchyma. Histological analysis also demonstrated that FUS can reduce neuron loss and blood vessel damage during brain abscess formation. Our findings indicate that the FUS system can achieve local reversible BBB opening, enhancing immunomodulation in an animal model of brain abscess.