Evaluation of Traumatic Spinal Cord Injury in a Rat Model Using Tc-GA-5 As a Potential In Vivo Tracer

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2021 Dec 10

PMID 34885718

Authors

Vanessa Izquierdo-Sanchez

Pablo C Zambrano-Rodriguez

Nadia Pena-Merino

Sirio Bolanos-Puchet

Horacio J Reyes-Alva

Angelina Martinez-Cruz

Sae Muniz-Hernandez

Gabriel Guizar-Sahagun

Luis Alberto Medina

Affiliations

Soon will be listed here.

Abstract

Spinal cord injury (SCI) refers to the damage suffered in the spinal cord by any trauma or pathology. The purpose of this work was to determine whether Tc-GA-5, a radiotracer targeting Glial Fibrillary Acidic Protein (GFAP), can reveal in vivo the reactivation of astrocytes in a murine model with SCI. A method for the Tc radiolabeling of the mouse anti-GFAP monoclonal antibody GA-5 was implemented. Radiochemical characterization was performed, and radioimmunohistochemistry assays were used to evaluate the integrity of Tc-GA-5. MicroSPECT/CT was used for in vivo imaging to trace SCI in the rats. No alterations in the GA-5's recognition/specificity ability were observed after the radiolabeling. The GA-5's radiolabeling procedure implemented in this work offers a practical method to allow the in vivo following of this monoclonal antibody to evaluate its biodistribution and specificity for GFAP receptors using SPECT/CT molecular imaging.

References

LeRoux L, Bredow S, Grosshans D, Schellingerhout D . Molecular imaging detects impairment in the retrograde axonal transport mechanism after radiation-induced spinal cord injury. Mol Imaging Biol. 2014; 16(4):504-10. PMC: 4085152. DOI: 10.1007/s11307-013-0713-0. View

Yuan Y, He C . The glial scar in spinal cord injury and repair. Neurosci Bull. 2013; 29(4):421-35. PMC: 5561940. DOI: 10.1007/s12264-013-1358-3. View

Okada S, Hara M, Kobayakawa K, Matsumoto Y, Nakashima Y . Astrocyte reactivity and astrogliosis after spinal cord injury. Neurosci Res. 2017; 126:39-43. DOI: 10.1016/j.neures.2017.10.004. View

Ahuja C, Wilson J, Nori S, Kotter M, Druschel C, Curt A . Traumatic spinal cord injury. Nat Rev Dis Primers. 2017; 3:17018. DOI: 10.1038/nrdp.2017.18. View

Hernandez J, Torres-Espin A, Navarro X . Adult stem cell transplants for spinal cord injury repair: current state in preclinical research. Curr Stem Cell Res Ther. 2011; 6(3):273-87. DOI: 10.2174/157488811796575323. View

Karimi-Abdolrezaee S, Billakanti R . Reactive astrogliosis after spinal cord injury-beneficial and detrimental effects. Mol Neurobiol. 2012; 46(2):251-64. DOI: 10.1007/s12035-012-8287-4. View

Song F, Tian M, Zhang H . Molecular imaging in stem cell therapy for spinal cord injury. Biomed Res Int. 2014; 2014:759514. PMC: 3950476. DOI: 10.1155/2014/759514. View

Orr M, Gensel J . Spinal Cord Injury Scarring and Inflammation: Therapies Targeting Glial and Inflammatory Responses. Neurotherapeutics. 2018; 15(3):541-553. PMC: 6095779. DOI: 10.1007/s13311-018-0631-6. View

Nestrasil I, Shapiro E, Svatkova A, Dickson P, Chen A, Wakumoto A . Intrathecal enzyme replacement therapy reverses cognitive decline in mucopolysaccharidosis type I. Am J Med Genet A. 2017; 173(3):780-783. PMC: 5367919. DOI: 10.1002/ajmg.a.38073. View

10.

Yang Z, Wang K . Glial fibrillary acidic protein: from intermediate filament assembly and gliosis to neurobiomarker. Trends Neurosci. 2015; 38(6):364-74. PMC: 4559283. DOI: 10.1016/j.tins.2015.04.003. View

11.

Albadawi H, Chen J, Oklu R, Wu Y, Wojtkiewicz G, Pulli B . Spinal Cord Inflammation: Molecular Imaging after Thoracic Aortic Ischemia Reperfusion Injury. Radiology. 2016; 282(1):202-211. PMC: 5207124. DOI: 10.1148/radiol.2016152222. View

12.

Lo W, Hsu C, Wu A, Yang L, Chen W, Chiu W . A novel cell-based therapy for contusion spinal cord injury using GDNF-delivering NIH3T3 cells with dual reporter genes monitored by molecular imaging. J Nucl Med. 2008; 49(9):1512-9. DOI: 10.2967/jnumed.108.051896. View

13.

Harkey 3rd H, White 4th E, Tibbs Jr R, Haines D . A clinician's view of spinal cord injury. Anat Rec B New Anat. 2003; 271(1):41-8. DOI: 10.1002/ar.b.10012. View

14.

Brenner M . Role of GFAP in CNS injuries. Neurosci Lett. 2014; 565:7-13. PMC: 4049287. DOI: 10.1016/j.neulet.2014.01.055. View

15.

Magaki S, Williams C, Vinters H . Glial function (and dysfunction) in the normal & ischemic brain. Neuropharmacology. 2017; 134(Pt B):218-225. PMC: 6132239. DOI: 10.1016/j.neuropharm.2017.11.009. View

16.

Wahl A, Correa D, Imobersteg S, Maurer M, Kaiser J, Augath M . Targeting Therapeutic Antibodies to the CNS: a Comparative Study of Intrathecal, Intravenous, and Subcutaneous Anti-Nogo A Antibody Treatment after Stroke in Rats. Neurotherapeutics. 2020; 17(3):1153-1159. PMC: 7609675. DOI: 10.1007/s13311-020-00864-z. View

17.

C Zambrano-Rodriguez P, Bolanos-Puchet S, Reyes-Alva H, Garcia-Orozco L, Romero-Pina M, Martinez-Cruz A . Micro-CT myelography using contrast-enhanced digital subtraction: feasibility and initial results in healthy rats. Neuroradiology. 2019; 61(3):323-330. DOI: 10.1007/s00234-019-02162-8. View

18.

Bradbury E, Burnside E . Moving beyond the glial scar for spinal cord repair. Nat Commun. 2019; 10(1):3879. PMC: 6713740. DOI: 10.1038/s41467-019-11707-7. View

19.

Baldwin S, Broderick R, Blades D, Scheff S . Alterations in temporal/spatial distribution of GFAP- and vimentin-positive astrocytes after spinal cord contusion with the New York University spinal cord injury device. J Neurotrauma. 1999; 15(12):1015-26. DOI: 10.1089/neu.1998.15.1015. View

20.

Ineichen B, Schnell L, Gullo M, Kaiser J, Schneider M, Mosberger A . Direct, long-term intrathecal application of therapeutics to the rodent CNS. Nat Protoc. 2016; 12(1):104-131. DOI: 10.1038/nprot.2016.151. View