Our laboratory studies the pathogenesis of intraventricular hemorrhage (IVH) and evaluates neuro-protective strategies to prevent brain injury after IVH in premature infants.  The major projects in our laboratory are focused on determining a) the mechanisms underlying white matter injury in premature infants with IVH and approaches to minimize the damage, b) the effect of IVH on glutamatergic neurogenesis and corticogenesis in the developing brain, and strategies to restore these processes, and c) the effect of prematurity on neurogenesis and corticogenesis.

To answer our research questions, we employ a preterm rabbit model (in vivo studies) and an in vitro organotypic forebrain slice culture model of IVH. Our glycerol model of IVH in preterm rabbits exhibits periventricular white matter injury and post-hemorrhagic hydrocephalus similar to that seen in human preterm survivors with IVH. In addition, we analyze autopsy samples from preterm infants with and without IVH. Commonly used techniques include Immunohistochemistry, confocal microscopy, stereological quantification of neural cells, Western blot analyses, real time qPCR, slice culture, neuronal migration studies, viral gene transfer, flow-cytometry, and magnetic bead isolation of cells.

Selected Bibliography:

1.Krishna S. Cheng B, Sharma D, Yadav S, Ballabh P. PPARg activation enhances myelination and neurological recovery in premature rabbits with intraventricular hemorrhage. PNAS in press 2021   

2. Ballabh P, de Vries LS. White matter injury in infants with intraventricular haemorrhage: mechanisms and therapies. Nat Rev Neurol. 2021 Apr;17(4):199-214. doi: 10.1038/s41582-020-00447-8. Epub 2021 Jan 27. PMID: 33504979

3. Cheng B, Ballabh P. Recovery of the brain after intraventricular hemorrhage. Semin Fetal Neonatal Med. 2021 Feb 26:101224. doi: 10.1016/j.siny.2021.101224. Online ahead of print. PMID: 33888444

4. Klebe D, Tibrewal M, Sharma DR, Vanparthy R, Krishna S, Varghese M Cheng B, Dobrenis K, Hof PR, Ballabh P.  Reduced hippocampal dendritic branchign , spine density and neurocognitive function in preamture infants and reversal with estrogen and TrkB agonist treatment. Cerebral Cortex 2019 Dec 17:29912):4832-4947  PMID: 308777

6.. Dohare P, Cheng B, Ahmed E, Yadala V, Singla P, Thomas S, Kayton R, Ungvari Z, Ballabh P. Glycogen synthase 3b inhibition enhances myelination in preterm rabbit newborns with intraventricular hemorrhage, but not recombinant Wnt3A. Neurobiol Dis. 2018 Jun 22;118:22-39. doi: 10.1016/j.nbd.2018.06.015.  PMID 29940337

7. Tibrewal M, Cheng B, Dohare P, Hu F, Mehdizadeh R, Wang P, Zheng D, Ungvari Z, Ballabh P. Disruption of interneuron neurogemeis in premature newborns and revesal with estrogen treatment. J Neurosci. 2018 Jan 31;38(5):1100-1113. doi: 10.1523/JNEUROSCI.1875-17.2017. Epub 2017 Dec 15. PMID: 29246927

8. Panda S, Dohare P, Jain S,XParikh N,  Singla P, Mehdizadeh R,  Klebe DW, Kleinman G, X Cheng B, Ballabh P. Estrogen treatment reverses prematurity-induced disruption in cortical interneuron population. Journal of Neuroscience. 2018 Aug 22;38(34):7378-7391. doi: 10.1523/JNEUROSCI.0478-18.2018. Epub 2018 Jul 23. PMID:30037831.

 (Society of Neuroscience selected this article to highlight the media under embargo).

9. Dohare P, Kidwai A, Kaur J, Singla P, Krishna S, Klebe D, Zhang X, Hevner R, Ballabh P.  GSK3β inhibition restores impaired neurogenesis in preterm neonates with intraventricular hemorrhage. Cereb Cortex. 2018 Sep 6. doi: 10.1093/cercor/bhy217. PMID: 30192926

10.  Dohare P, Zia MT, Ahmed E, Ahmed A, Yadala V, Schober AL, Ortega JA, Kayton R, Ungvari Z, Mongin AA, Ballabh P. AMPA-Kainate Receptor Inhibition Promotes Neurologic Recovery in Premature Rabbits with Intraventricular Hemorrhage. J Neurosci. 2016 Mar 16;36(11):3363-77. doi: 10.1523/JNEUROSCI.4329-15.2016. PMID: 26985043

11. Vinukonda G, Dohare P, Arshad A, Zia MT, Panda S, Korumilli R, Kayton R, Hascall VC, Lauer ME, Ballabh P. Hyaluronidase and Hyaluronan Oligosaccharides Promote Neurological Recovery after Intraventricular Hemorrhage. J Neurosci. 2016 Jan 20;36(3):872-89. doi: 10.1523/JNEUROSCI.3297-15.2016.

12 Vinukonda G, Hu F, Mehdizadeh R. Kayton R, Ballabh P. Epidermal growth factor preserves myelin and promotes astrogliosis after intraventricular hemorrhage. Glia. 2016 Jul 29. doi: 10.1002/glia.23037. PMID: 27472419

13. Arshad A, Vose LR, Vinukonda G, Hu V, Yoshikawa K, Csiszar A, Brumberg J, Ballabh P. Extended production of cortical interneurons into the third trimester of human gestation. Cerebral cortex. 2015 Apr 16. PMID: 25882040

14. Vose LR, Vinukonda G, Jo S, Miry O, Diamond D, Korumilli R, Arshad A, Zia MT, Hu F, Kayton RJ, La Gamma EF, Bansal R, Bianco AC, Ballabh, P. Treatment with thyroxine restores myelination and clinical recovery after intraventricular hemorrhage. J Neurosci. 2013 Oct 30;33(44):17232-46

15. Malik S, Vinukonda G, Vose LR, Diamond D, Bhimavarapu BB, Hu F, Zia MT, Hevner R, Zecevic N, Ballabh P. Neurogenesis continues in the third trimester of pregnancy and is suppressed by premature birth. J Neurosci. 2013 Jan 9;33(2):411-23. PMID: 23303921

16. Dummula K, Vinukonda G, Chu P, Xing Y, Hu F, Mailk S, Csiszar A, Chua C, Mouton P, Kayton RJ, Brumberg JC, Bansal R, Ballabh P. Bone morphogenetic protein inhibition promotes Neurological recovery after intraventricular hemorrhage. J Neurosci. 2011 Aug 24;31(34):12068-82. PubMed. PMID:21865450; PubMed Central PMCID: PMC3167068.

17. Vinukonda G, Csiszar, A, Hu F, Dummula K, Pandey NK, Zia MT, Ferreri, NR, Ungvari, Z, LaGamma, EF, Ballabh, P. Neuroprotection in intraventricular hemorrhage by cox-2 inhibition: EP1 receptor and TNF-α are downstream mediators of brain injury. Brain 2010 Aug;133(Pt 8):2264-802.

18. Chua C, Chahboune H, Braun A, Dummula K, Chua CE, Yu J, Ungvari Z, Sherbany A, Hyder F, Ballabh P. Consequences of intraventricular hemorrhage in a rabbit pup model. Stroke 2009 Oct;40(10):3369-77. 

19. Vinukonda G. Csiszar, A. Hu F, Dummula K, Pandey NK, Zia MT, Ferreri, NR, Ungvari, Z, LaGamma, EF, Ballabh, P. Effect of prenatal glucocorticoid on the vasculature of the developing brain. Stroke. 2010 Aug;41(8):1766-73. PubMed PMID:20616316; PubMed Central PMCID: PMC2920046.

20. Ballabh P, Xu H, Hu F, Xu H, Braun A, Ungvari Z. Csiszar A, Goldman S, Nedergaard M. Angiogenic inhibition reduced germinal matrix hemorrhage. Nature Medicine 2007 Apr;13(4):477-85. (Cover page article). 

21. Braun A, Xu H, Kocherlakota P, Siegel D, Ungvari Z. Csiszar A , Nedergaard M, Ballabh P. Paucity of pericytes in germinal matrix vasculature. J Neurosci 2007 Oct 31; 27(44):12012-12024.

22. Ballabh P, Braun A, Nedergaard M. Recent insights in blood brain barrier: an overview. Structure, regulation, modulating factors and clinical implications. Neurobiology of Disease 2004;16:1-13.

Lab Website: https://ballabhlab.einsteinmedneuroscience.org/