Maintaining unperturbed cerebral blood flow is key in the study of brain metastasis and its interactions with stress and inflammatory responses
| Autor: | Amit Benbenishty, Pablo Blinder, Lee Shaashua, Niva Segev-Amzaleg, Shamgar Ben-Eliyahu, Rivka Melamed |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
Pathology medicine.medical_specialty Surgical stress Immunology External carotid artery Brain tumor Inflammation Article 03 medical and health sciences Behavioral Neuroscience Mice 0302 clinical medicine Stress Physiological medicine.artery medicine Animals Common carotid artery Endocrine and Autonomic Systems business.industry Brain Neoplasms Brain Blood flow medicine.disease Cerebral blood flow Blood-Brain Barrier 030220 oncology & carcinogenesis Cerebrovascular Circulation medicine.symptom business 030217 neurology & neurosurgery Brain metastasis |
| Popis: | Blood-borne brain metastases are associated with poor prognosis, but little is known about the interplay between cerebral blood flow, surgical stress responses, and the metastatic process. The intra-carotid inoculation approach, traditionally used in animal studies, involves permanent occlusion of the common carotid artery (CCA). Herein we introduced a novel intra-carotid inoculation approach that avoids CCA ligation, namely - assisted external carotid artery inoculation (aECAi) - and compared it to the traditional approach in C57/BL6 mice, assessing cerebral blood flow; particle distribution; blood-brain barrier (BBB) integrity; stress, inflammatory and immune responses; and brain tumor retention and growth. Doppler flowmetry and two-photon imaging confirmed that only in the traditional approach regional and capillary cerebral blood flux were significantly reduced. Corticosterone and plasma IL-6 levels were higher in the traditional approach, splenic numbers of NK, CD3+, granulocytes, and dendritic cells were lower, and many of these indices were more profoundly affected by surgical stress in the traditional approach. BBB integrity was unaffected. Administration of spherical beads indicated that CCA ligation significantly limited brain distribution of injected particles, and inoculation of D122-LLC syngeneic tumor cells resulted in 10-fold lower brain tumor-cell retention in the traditional approach. Last, while most of the injected tumor cells were arrested in extra-cranial head areas, our method improved targeting of brain-tissue by 7-fold. This head versus brain distribution difference, commonly overlooked, cannot be detected using in vivo bioluminescent imaging. Overall, it is crucial to maintain unperturbed cerebral blood flow while studying brain metastasis and interactions with stress and inflammatory responses. |
| Databáze: | OpenAIRE |
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