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Sujatha Kannan, MD

Anesthesiology and Critical Care Medicine

Johns Hopkins University School of Medicine


Kennedy Krieger Institute
Baltimore, MD 21287

Phone : (410) 955-6412
Email: skannan3@jhmi.edu
Curriculum Vitae: CV(pdf)

Imaging and Targeted therapy in maternal inflammation induced perinatal brain injury


Brain injury is a major cause of morbidity and mortality in the perinatal period. Intrauterine infection is known to be a risk factor for brain damage in the neonate irrespective of the gestational age. Intrauterine infection may lead to a fetal systemic inflammatory response mediated by cytokines that has been implicated in the development of periventricular leukomalacia (PVL) leading to lifelong disabilities such as cerebral palsy and cognitive impairment in the infant. While in recent years a number of in vitro and in vivo studies have implicated microglial cells in the development of PVL in hypoxic-ischemic brain injuries, there is a knowledge gap in understanding and recognizing the progression of the cellular events leading to white matter injury. Lack of such knowledge is a critical problem because it prevents designing of effective therapy for arresting the progression of brain injury. The long-term goal of this research group is to understand the mechanism and progression of the cellular and metabolic derangements leading to brain injury during development, and to use this information to design specific targeted therapy using novel nanopolymers. The central hypothesis is that the fetal inflammatory response following endotoxin induced intra-uterine inflammation leads to activation and recruitment of microglial cells in the fetal brain that progresses over time with widespread production of pro-inflammatory mediators leading to the death of oligodendrocytes and white matter injury, and inhibiting the microglial cells will arrest this process. This work is done using a rabbit model of neuroinflammation and cerebral palsy induced by maternal intra-uterine endotoxin administration. Imaging of neuroinflammation and white matter injury is done using PET and MRI. Drugs are targeted to activated microglial cells using dendrimers for suppressing neuroinflammation and attenuation of white matter injury.



 

Relevent References

Animal Model and Imaging
 
  1. Kannan S, Saadani-Makki F, Muzik O, Chakraborty P, Mangner TJ, Janisse J, Romero R, Chugani D. Microglial activation in perinatal rabbit brain induced by intrauterine inflammation: Detection with [11C](R)-PK11195 and microPET, Journal of Nuclear Medicine, 48(6), 946-54, 2007.
     
  2. Saadani-Makki F*, Kannan S, Lu X, Janisse J, Dawe E, Edwin S, Romero R, Chugani D. Intrauterine administration of endotoxin leads to motor deficits in a rabbit model: a link between prenatal infection and cerebral palsy., AJOG, 199(6), Pages 651.e1-651.e7
     
  3. Kannan S*, Saadani-Makki F, Balakrishnan B, Dai H, Chakraborty P, Janisse J, Muzik O, Romero. R, Chugani D. Decreased cortical serotonin in neonatal rabbits exposed to endotoxin in utero. In press, Journal of cerebral Blood Flow and Metabolism, 2010.
     

Dendrimer-based targeted delivery
 
  1. Perumal OP*, Inapagolla R*, Kannan S, Kannan RM. The effect of surface functionality on cellular trafficking of dendrimers. Biomaterials. 2008 Aug-Sep;29(24-25):3469-76.
     
  2. H.Dai, R.Navath, B.Balakrishnan, B.Raja Guru, M.Mishra, R.Romero, R.M.Kannan*, S.Kannan*. Intrinsic targeting of neuroinflammation by polyamidoamine dendrimers in a rabbit model of cerebral palsy, In press, Future Medicine:Nanomedicine,Aug. (2010)
     
  3. Wang B*, Navath R, Romero R, Kannan S, Kannan R. Anti-inflammatory and anti-oxidant activity of anionic dendrimer-N-acetyl cysteine conjugates in activated microglial cells. Int J Pharm. 2009 Jul 30;377(1-2):159-68.
     
  4. B. Wang, R.Navath, A.Menjoge, B.Balakrishnan, R.Bellair, H.Dai, R.Romero, S.Kannan, R.M.Kannan*, Inhibition of bacterial growth and intramniotic infection in a guinea pig model of chorioamnionitis using PAMAM dendrimers, doi:10.1016/j.ijpharm.2010.05.030, Int.J. Pharm., May (2010)