All Publications


  • Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation. Cell Fernández-Castañeda, A., Lu, P., Geraghty, A. C., Song, E., Lee, M. H., Wood, J., O'Dea, M. R., Dutton, S., Shamardani, K., Nwangwu, K., Mancusi, R., Yalçın, B., Taylor, K. R., Acosta-Alvarez, L., Malacon, K., Keough, M. B., Ni, L., Woo, P. J., Contreras-Esquivel, D., Toland, A. M., Gehlhausen, J. R., Klein, J., Takahashi, T., Silva, J., Israelow, B., Lucas, C., Mao, T., Peña-Hernández, M. A., Tabachnikova, A., Homer, R. J., Tabacof, L., Tosto-Mancuso, J., Breyman, E., Kontorovich, A., McCarthy, D., Quezado, M., Vogel, H., Hefti, M. M., Perl, D. P., Liddelow, S., Folkerth, R., Putrino, D., Nath, A., Iwasaki, A., Monje, M. 2022

    Abstract

    COVID survivors frequently experience lingering neurological symptoms that resemble cancer-therapy-related cognitive impairment, a syndrome for which white matter microglial reactivity and consequent neural dysregulation is central. Here, we explored the neurobiological effects of respiratory SARS-CoV-2 infection and found white-matter-selective microglial reactivity in mice and humans. Following mild respiratory COVID in mice, persistently impaired hippocampal neurogenesis, decreased oligodendrocytes, and myelin loss were evident together with elevated CSF cytokines/chemokines including CCL11. Systemic CCL11 administration specifically caused hippocampal microglial reactivity and impaired neurogenesis. Concordantly, humans with lasting cognitive symptoms post-COVID exhibit elevated CCL11 levels. Compared with SARS-CoV-2, mild respiratory influenza in mice caused similar patterns of white-matter-selective microglial reactivity, oligodendrocyte loss, impaired neurogenesis, and elevated CCL11 at early time points, but after influenza, only elevated CCL11 and hippocampal pathology persisted. These findings illustrate similar neuropathophysiology after cancer therapy and respiratory SARS-CoV-2 infection which may contribute to cognitive impairment following even mild COVID.

    View details for DOI 10.1016/j.cell.2022.06.008

    View details for PubMedID 35768006

  • First reported use of real-time intraoperative computed tomography angiography image registration using the Machine-vision Image Guided Surgery system: illustrative case. Journal of neurosurgery. Case lessons Wadhwa, H., Malacon, K., Medress, Z. A., Leung, C., Sklar, M., Zygourakis, C. C. 2021; 1 (18): CASE2125

    Abstract

    Vertebral artery injury is a devastating potential complication of C1-2 posterior fusion. Intraoperative navigation can reduce the risk of neurovascular complications and improve screw placement accuracy. However, the use of intraoperative computed tomography (CT) increases radiation exposure and operative time, and it is unable to image vascular structures. The Machine-vision Image Guided Surgery (MvIGS) system uses optical topographic imaging and machine vision software to rapidly register using preoperative imaging. The authors presented the first report of intraoperative navigation with MvIGS registered using a preoperative CT angiogram (CTA) during C1-2 posterior fusion.MvIGS can register in seconds, minimizing operative time with no additional radiation exposure. Furthermore, surgeons can better adjust for abnormal vertebral artery anatomy and increase procedure safety.CTA-guided navigation generated a three-dimensional reconstruction of cervical spine anatomy that assisted surgeons during the procedure. Although further study is needed, the use of intraoperative MvIGS may reduce the risk of vertebral artery injury during C1-2 posterior fusion.

    View details for DOI 10.3171/CASE2125

    View details for PubMedID 35855470

    View details for PubMedCentralID PMC9245760

  • Internal state configures olfactory behavior and early sensory processing in Drosophila larvae SCIENCE ADVANCES Vogt, K., Zimmerman, D. M., Schlichting, M., Hernandez-Nunez, L., Qin, S., Malacon, K., Rosbash, M., Pehlevan, C., Cardona, A., Samuel, A. T. 2021; 7 (1)
  • Sex differences in microglia as a risk factor for Alzheimer's disease Sex and Gender Differences in Alzheimer's disease Delage , C., Rendina , D. N., Malacon , K. E., Tremblay , M., Bilbo , S. D. Elsevier Inc.. 2021; 1: 79-104
  • Neonatal immune challenge induces female-specific changes in social behavior and somatostatin cell number BRAIN BEHAVIOR AND IMMUNITY Smith, C. J., Kingsbury, M. A., Dziabis, J. E., Hanamsagar, R., Malacon, K. E., Tran, J. N., Norris, H. A., Gulino, M., Bordt, E. A., Bilbo, S. D. 2020; 90: 332–45

    Abstract

    Decreases in social behavior are a hallmark aspect of acute "sickness behavior" in response to infection. However, immune insults that occur during the perinatal period may have long-lasting consequences for adult social behavior by impacting the developmental organization of underlying neural circuits. Microglia, the resident immune cells of the central nervous system, are sensitive to immune stimulation and play a critical role in the developmental sculpting of neural circuits, making them likely mediators of this process. Here, we investigated the impact of a postnatal day (PND) 4 lipopolysaccharide (LPS) challenge on social behavior in adult mice. Somewhat surprisingly, neonatal LPS treatment decreased sociability in adult female, but not male mice. LPS-treated females also displayed reduced social interaction and social memory in a social discrimination task as compared to saline-treated females. Somatostatin (SST) interneurons within the anterior cingulate cortex (ACC) have recently been suggested to modulate a variety of social behaviors. Interestingly, the female-specific changes in social behavior observed here were accompanied by an increase in SST interneuron number in the ACC. Finally, these changes in social behavior and SST cell number do not appear to depend on microglial inflammatory signaling, because microglia-specific genetic knock-down of myeloid differentiation response protein 88 (MyD88; the removal of which prevents LPS from increasing proinflammatory cytokines such as TNFα and IL-1β) did not prevent these LPS-induced changes. This study provides novel evidence for enduring effects of neonatal immune activation on social behavior and SST interneurons in females, largely independent of microglial inflammatory signaling.

    View details for DOI 10.1016/j.bbi.2020.08.013

    View details for Web of Science ID 000577976900031

    View details for PubMedID 32860938

    View details for PubMedCentralID PMC7556772